DOCSLIB.ORG

1 PHA 5127 Answers Homework 4 Jeff Stark 1. What Is the Maximum

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
1 PHA 5127 Answers Homework 4 Jeff Stark 1. What Is the Maximum PHA 5127 Answers Homework 4 Jeff Stark 1. What is the maximum extraction ratio for renal filtration if neither reabsorption nor active secretion take place? Explain. The drug enters the kidney at the rate of renal blood flow (RBF), 1200 ml/min. The rate of filtration for a drug depends on the glomerular filtration rate (GFR) and the unbound fraction of drug in the plasma (fu). The extraction ratio for the kidney when filtration is the only renal process occurring is: GFR × fu E = Re n RBF The maximum extraction ratio is observed when there is no protein binding, fu=1. In this situation, 125ml / min×1.0 E = = 0.10 Re n 1200ml / min Thus, about 10% of the drug entering the kidneys is filtered through the glomerular capillaries. 2. The renal clearances and the fractions unbound to plasma proteins of three drugs in a 70kg 40 year old man are listed as follows: Renal Clearance (ml/min) Fraction Unbound Drug 1 62.5 0.5 Drug2 30 0.01 Drug3 0.45 0.3 Explain the likely contribution of filtration, secretion, and reabsorption to the renal handling of each of these drugs. Assume a GFR of 125 ml/min and a urine flow of 1.5 ml/min. When approaching problems such as this, ask yourself what the renal clearance would be if you have only filtration taking place. This is a good starting point and will give you some idea of the relative magnitude of secretion and reabsorption as well. Drug 1. If only glomerular filtration occurs, Clren = GFR·fu = 125 ml/min·0.5 = 62.5 ml/min D:\Homeworks\Homework4\Fall-99\ans-hw-4-99.doc 1 Since the renal clearance of this drug is stated as 62.5 ml/min, we may conclude (I) that glomerular filtration is the only renal process involved or (ii) that active secretion and tubular reabsorption occur at the same rate. Recall: Clren ~ Clfiltration + Clsecretion + Clurine flow - reabsorption Drug 2 Clfiltration = 125 ml/min · 0.01 = 1.25 ml/min The clearance due to glomerular filtration of this drug is very small since it is highly protein- bound (only free drug is filtered). The renal clearance is given to be 30 ml/min, much larger than clearance due only to filtration. We may conclude that active secretion occurs in addition to filtration. If tubular reabsorption occurs, the amount absorbed is outweighed by the process of active secretion. Drug 3 Clfiltration = 125 ml/min · 0.3 = 37.5 ml/min For drug 3, renal clearance is 0.45 ml/min. Since this value is so small compared to the clearance due to filtration, we may conclude that there is a large degree of tubular reabsorption. For some drugs, tubular reabsorption occurs to such a high degree that the only drug eliminated in the kidneys is that lost in normal urine flow, Clurine flow = urine flow · fu = 1.5 ml/min · 0.3 = 0.45 ml/min Since this value is equal to the renal clearance given, we may conclude that "complete" reabsorption takes place and drug lost in the urine flow is the only effective process of renal clearance. 3. A 5'10" 40 year old 90kg man has a serum creatinine level of 1.5 mg/100 ml and is being treated with aminoglycosides. Estimate the clearance for the aminoglycoside and the half-life for this patient. If the desired peak plasma level is 6 mg/L and the volume of distribution is 0.24 L/kg (IBW), what dose should be given (just consider one dose). How long will it take to reach a plasma level of 1 mg/L. D:\Homeworks\Homework4\Fall-99\ans-hw-4-99.doc 2 Given Information · 5'10" tall male · 90 kg · Scr = 1.5 mg/100ml Estimate clearance of aminoglycosides and t1/2 for this patient. For aminoglycosides, ClCreatinine » ClAminoglycosides since these compounds are eliminated only by filtration and protein binding is minimal. The empirical equation for creatinine clearance is (140 - age) × weight ClCreat (male) = [units : ml/min ] 72 × CpCreat Weight in this equation is ideal body weight (IBW). For males IBW is calculated by IBW = 50 kg + 2.3 kg for each inch over 5 ft in height = 50 kg + 2.3 kg · 10 = 73 kg Clcreat may now be calculated: (140 - 40) × (73) Cl = Creat (72) × (1.5) = 67.6 ml/min Since Clcreat is related to the glomerular filtration rate (GFR), we know that there is some renal failure in the patient (normal GFR = 125 ml/min). The aminoglycoside t1/2 may be calculated easily after ke is determined. For aminoglycosides, -1 k e = 0.00293× ClCreat + 0.014 [units : hr ] = (0.00293)·(67.6) + 0.014 = 0.212 hr-1 The half-life is then ln 2 0.693 t1/ 2 = = -1 = 3.3hr ke 0.212 To obtain a peak plasma concentration of 6 mg/L, what dose should be given? Assuming the infusion time is sufficiently short and IV bolus equations are adequate approximations, D:\Homeworks\Homework4\Fall-99\ans-hw-4-99.doc 3 D Cp0 = Vd Solving for dose D gives D = Cp0 ×Vd = (6 mg/L)·(0.24 L/kg)·(90kg) = 130 mg How long will it take to reach a plasma concentration of 1 mg/L? For and IV bolus injection, -ke ×t Cp(t) = Cp0 × e In this equation, Cp0 is the initial plasma concentration (6mg/L), Cp(t) is the concentration at any later time point, and t is the time after injection. Solving for t gives: Cp(t) = e -ket Cp0 æ Cp(t) ö lnç ÷ = -k t ç ÷ e è Cp0 ø 1 æ Cp(t) ö t = - lnç ÷ ke è Cp0 ø 1 æ 1mg / L ö = - lnç ÷ -1 ç ÷ 0.212hr è 6mg / L ø = 8.5 hr 4. What are the assumptions made by the one-compartment model? · Instantaneous distribution · Linear kinetics (AUC µ Dose) D:\Homeworks\Homework4\Fall-99\ans-hw-4-99.doc 4 5. Mark the following statements true (T) or false (F): T F The maximum value which renal clearance can approach is 1200 ml/min. T F Large drug molecules and low degree of protein binding could predispose a drug to glomerular filtration. T F Tubular secretion may be a competitive process. T F Tubular reabsorption can only be a passive transport process. T F Highly ionized drugs tend to have more tubular reabsorption. T F Molecular size, protein binding, and lipid solubility significantly influence glomerular filtration. T F Urinary excretion of amphetamine can be decreased by raising pH. T F With first-order elimination, the fraction of a drug in the body eliminated over a given time depends on the drug concentration. Use the Excel Spreadsheets available to draw the Cp vs time curves for the following inputs. Use the IV-S.xls for the first two (one compartment, i.v. bolus, single dose) and Oral.xls for the third (one compartment, oral, single). Calculate and record the missing parameters and explain the results. 1. Input Results D[mg] 120 120 Peak(mg/L) 1.20 1.20 Vd(L) 100 100 Ke(1/h) 0.12 0.24 CL(L/h) 12 24 t1/2(h) 2.8 2.9 AUC(mg/L·h) 10.00 5.00 1.4 1.2 1 0.8 0.6 0.4 0.2 0 0 10 20 30 D C = e -ket Vd D:\Homeworks\Homework4\Fall-99\ans-hw-4-99.doc 5 2. Input Results D[mg] 180 60 Peak (mg/L) 1.80 0.60 Vd(L) 100 100 Ke(1/h) 0.24 0.24 CL(L/h) 24 24 t1/2 (h) 2.9 2.9 AUC(mg/L*h) 7.50 2.50 2 1.5 1 0.5 0 0 10 20 30 D C = e -ket Vd 3. Input Results D[mg] 60 60 tmax (h) 1.53 2.01 Bioavail. 1 1 Peak(mg/L) 0.65 0.40 Ka(1/h) 1 1 Ke(1/h) 0.4 0.2 Vd(L) 50 100 t1/2 (h) 1.73 3.47 CL(L/h) 20 20 AUC(mg/L*h) 3.00 3.00 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0 6 12 18 24 30 f × D × k Cp = a (e -ket - e -kat ) Vd (ka - ke ) D:\Homeworks\Homework4\Fall-99\ans-hw-4-99.doc 6.
Load more

Recommended publications
  • Note on the Interpretation of Clearance Methods in the Diseased Kidney
    NOTE ON THE INTERPRETATION OF CLEARANCE METHODS IN THE DISEASED KIDNEY Homer W. Smith J Clin Invest. 1941;20(6):631-635. https://doi.org/10.1172/JCI101256. Research Article Find the latest version: https://jci.me/101256/pdf NOTE ON THE INTERPRETATION OF CLEARANCE METHODS IN THE DISEASED KIDNEY By HOMER W. SMITH (From the Department of Physiology, New York University CoUlege of Medicine, New York City) (Received for publication June 16, 1941) In interpreting the results obtained by clear- but only by investigation; but since by definition they are ance methods in the diseased kidney, the physio- unable to excrete diodrast they do not contribute to CD or TmD. logical limitations of these methods must be kept All renal parenchyma which normally lacks excretory clearly in mind. Since there has been no oppor- function, or which has lost its excretory function, will be tunity to discuss these limitations generally, it designated as inert tissue. This would include capsular has seemed desirable to emphasize certain more and connective tissue, impotent nephrons as defined above, important points in this note. injured nephrons which permit the back-diffusion of inulin and other constituents of the tubular urine, nephrons which The four methods to be considered here are are obstructed by casts or disconnected from collecting the inulin clearance (CIN), the plasma diodrast ducts so that urine formation is impossible, and fibrotic clearance (CD), the maximal rate of tubular ex- glomeruli and tubular fragments generally. cretion of diodrast (TmD) and the maximal rate of tubular reabsorption of glucose (TmG), all Total renal function and function in four methods being based on overall measure- individual nephrons ments made on the two kidneys by the collection Recognizing that there are two million-odd of bladder urine (4, 10, 12).
    [Show full text]
  • Dmd.117.077586.Full.Pdf
    DMD Fast Forward. Published on November 21, 2017 as DOI: 10.1124/dmd.117.077586 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 77586 Discovery and Validation of Pyridoxic Acid and Homovanillic Acid as Novel Endogenous Plasma Biomarkers of Organic Anion Transporter (OAT) 1 and OAT3 in Cynomolgus Monkeys Downloaded from dmd.aspetjournals.org Hong Shen, David M. Nelson, Regina V. Oliveira, Yueping Zhang, Colleen A. Mcnaney, Xiaomei Gu, Weiqi Chen, Ching Su, Michael D. Reily, Petia A. Shipkova, Jinping Gan, Yurong Lai, Punit Marathe, and W. Griffith Humphreys at ASPET Journals on September 29, 2021 Departments of Metabolism and Pharmacokinetics (H.S., Y.Z., X.G., W.C., J.G., Y.L., P.M., W.G.H.), Discovery Toxicology (D.N., C.A.M., M.D.R.), Bioanalytical Research (R.O., P.A.S.), and Discovery Pharmaceutics (C.S.), Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543, United States 1 DMD Fast Forward. Published on November 21, 2017 as DOI: 10.1124/dmd.117.077586 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 77586 Running title: Identification of functional plasma markers of OAT1 and OAT3 in vivo Address correspondence to: Dr. Hong Shen Department of Metabolism and Pharmacokinetics (MAP) Pharmaceutical Candidate Optimization (PCO) Downloaded from Bristol-Myers Squibb Company (BMS) Route 206 & Province Line Road, Princeton, NJ 08543-4000 Telephone: (609) 252-4509 dmd.aspetjournals.org Facsimile: (609) 252-6802 E-mail: [email protected] at ASPET Journals on September 29, 2021 Number of text pages: 29 Number of tables: 3 Number of figures: 6 Number of references: 39 Number of words: Abstract: 249 Introduction: 794 Discussion: 1832 Abbreviations: Ae, amount of unchanged drug recovered in the urine; AUC, area under the plasma concentration-time curve; CCK-8, cholecystokinin octapeptide; CE, collision energy; CLNR, 2 DMD Fast Forward.
    [Show full text]
  • Acute Blood Loss
    Therapeutics in Practice Acute Blood Loss Column Editor K. Gary Magdesian, DVM, DACVIM, DACVECC, DACVCP University of California, Davis Debra Deem Morris, DVM, MS, DACVIM Acute hemorrhage, a form of hypovolemic shock, can result from external or internal 190 State Route 10 blood loss. Distinguishing between these two types of hemorrhage is important to ren - dering proper therapy because cases of controllable hemorrhage must be treated differ - East Hanover, NJ 07936 ently than cases of uncontrollable hemorrhage. • phone 973-599-1191 • fax 973-599-1193 PATHOPHYSIOLOGY OF HEMORRHAGIC SHOCK • email stretchdee m@ yahoo.com Acute hemorrhage results in hypovolemia and a reduction in oxygen-carrying capac - ity (hemoglobin). A blood volume loss of 15% to 20% is clinically detectable, while life-threatening circulatory failure occurs with a blood volume loss of 30% to 40%. 1 Compensatory physiologic mechanisms include vasoconstriction, increased cardiac contractility, and tachycardia (activation of the sympathetic nervous system). In addi - tion, the drop in hydrostatic pressure due to hypovolemia causes filtration fraction to diminish and lymphatic flow to increase as a result of sympathetic activation and a reduction in central venous pressure (CVP). These changes result in a net movement of interstitial fluid into the vascular space. Simultaneously, the renin–angiotensin– aldosterone system is activated, resulting in a decreased glomerular filtration rate, decreased urine production and enhanced renal sodium resorption, increased thirst, and vasoconstriction. Vasopressin contributes to vasoconstriction and thirst. These compensatory mechanisms can maintain circulation in cases of mild blood loss (up to a volume loss of 15%). Losses exceeding this amount require volume replacement and are beyond physiologic compensation.
    [Show full text]
  • 1) an Increase in the Concentration of Plasma Potassium Causes Increase I
    Select the one that is the best answer: 1) An increase in the concentration of plasma potassium causes increase in : a) release of renin b) secretion of aldosterone c) secretion of ADH d) release of natriuretic hormone e) production of angiotensin II . 2) Amino acids are almost completely reabsorbed from the glomerular filtrate via active transport in the : a) proximal tubule b) loop of Henle c) distal tubule d) collecting duct e) renal pelvis 3) Glomerular filtration rate would be increased by : a) constriction of the afferent arteriole b) a decrease in afferent arteriolar pressure c) compression of the renal capsule d) a decrease in the concentration of plasma protein e) a decrease in renal blood flow 4) The greatest amount of hydrogen ion secreted by the proximal tubule is associated with : a) excretion of potassium ion b) excretion of hydrogen ion c) reabsorption of calcium ion d) reabsorption of bicarbonate ion e) reabsorption of phosphate ion 5) In controlling the synthesis and secretion of aldosterone , which of the following factors is least important ? a) renin b) angiotensin II c) concentration of plasma Na+ d) concentration of plasma K+ e) adrenocorticotropic hormone ( ACTH ) 6) Renal correction of acute hyperkalemia will result in : a) alkalosis b) acidosis - c) increased secretion of HCO3 d) increased secretion of H+ e) increased secretion of Na+ 7) Most of the glucose that is filtered through the glomerulus undergoes reabsorption in the : a) proximal tubule b) descending limp of the loop of Henle c) ascending limb of the loop of Henle d) distal tubule e) collecting duct 8) Ammonia is an affective important urinary buffer for which of the following reasons : a) its production in the kidney decrease during chronic acidosis b) the walls of the renal tubules are impermeable to NH3 c) the walls of the renal tubules are impermeable to NH3 d) its acid base reaction has a low pKa e) none of the above .
    [Show full text]
  • Download (7MB)
    https://theses.gla.ac.uk/ Theses Digitisation: https://www.gla.ac.uk/myglasgow/research/enlighten/theses/digitisation/ This is a digitised version of the original print thesis. Copyright and moral rights for this work are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This work cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Enlighten: Theses https://theses.gla.ac.uk/ [email protected] The Development of HPLC Methods for the Determination of Methotrexate and Doxorubicin Metabolites and their Application to Clinical Studies. Yahya Yahya Zeki Farid BSc PhD University of Glasgow Department of Pathological Biochemistry Faculty of Medicine JUNE 1983 X s. HERON LTD 5 QUEENS CRESCENT ST. GEORGES CROSS GLASGOW 041 332 1883 ProQuest Number: 10646152 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uesL ProQuest 10646152 Published by ProQuest LLO (2017). Copyright of the Dissertation is held by the Author.
    [Show full text]
  • Relationship Between Renin and Intrarenal Hemodynamics in Hemorrhagic Hypotension
    Relationship between renin and intrarenal hemodynamics in hemorrhagic hypotension A. Grandchamp, … , J. R. Scherrer, B. Truniger J Clin Invest. 1971;50(5):970-978. https://doi.org/10.1172/JCI106590. Research Article In order to investigate the possible role of the renin-angiotensin system in the regulation of intrarenal hemodynamics in hemorrhagic hypotension (HH), seven mongrel dogs have been studied under the following conditions: (a) Control, (b) HH (mean arterial pressure 70 mm Hg), and (c) HH + alpha adrenergic blockade by phenoxybenzamine (HH + POB). The following parameters were obtained for the right kidney: Intrarenal distribution of blood flow and local blood flow rates (133Xe washout technique); total renal blood flow (RBF) on the basis of the clearance and extraction ratio of PAH and the arterial hematocrit; plasma renin concentrations in the renal artery and vein by the method of Boucher and his associates; and renin release into the renal circulation. Alpha adrenergic blockade reverted the typical redistribution of intrarenal blood flow observed under HH. In hemorrhage, arterial and venous renin concentrations increased by a factor of 3.4 and 4.8 respectively. A further small increase was observed during HH + POB with the respective factors increasing to 4.8 and 5.3, as compared with control values. The renin release into the circulation increased by a factor of 1.2 in HH and 4.0 in HH + POB. Whereas in HH there seemed to be a relationship between increased renin concentrations or renin release, and the redistribution of blood flow, no such correlation was found […] Find the latest version: https://jci.me/106590/pdf Relationship between Renin and Intrarenal Hemodynamics in Hemorrhagic Hypotension A.
    [Show full text]
  • Discovery and Validation of Pyridoxic Acid and Homovanillic Acid As
    Supplemental material to this article can be found at: http://dmd.aspetjournals.org/content/suppl/2017/11/21/dmd.117.077586.DC1 1521-009X/46/2/178–188$25.00 https://doi.org/10.1124/dmd.117.077586 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 46:178–188, February 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Discovery and Validation of Pyridoxic Acid and Homovanillic Acid as Novel Endogenous Plasma Biomarkers of Organic Anion Transporter (OAT) 1 and OAT3 in Cynomolgus Monkeys s Hong Shen, David M. Nelson, Regina V. Oliveira, Yueping Zhang, Colleen A. Mcnaney, Xiaomei Gu, Weiqi Chen, Ching Su, Michael D. Reily, Petia A. Shipkova, Jinping Gan, Yurong Lai, Punit Marathe, and W. Griffith Humphreys Departments of Metabolism and Pharmacokinetics (H.S., Y.Z., X.G., W.C., J.G., Y.L., P.M., W.G.H.), Discovery Toxicology (D.M.N.), Bioanalytical and Discovery Analytical Sciences (R.V.O., C.A.M., M.D.R., P.A.S.), and Discovery Pharmaceutics (C.S.), Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, Princeton, New Jersey Received July 14, 2017; accepted November 17, 2017 Downloaded from ABSTRACT Perturbation of organic anion transporter (OAT) 1- and OAT3- animals. The plasma of animals was then subjected to targeted mediated transport can alter the exposure, efficacy, and safety of LC-MS/MS analysis, which confirmed that the PDA and HVA AUCs drugs. Although there have been reports of the endogenous increased by approximately 2- to 3-fold by PROB pretreatments. biomarkers for OAT1/3, none of these have all of the characteristics PROB also increased the plasma concentrations of hexadecane- dmd.aspetjournals.org required for a clinical useful biomarker.
    [Show full text]
  • Clearance Concepts Ln the Kidney
    CLEARANCE CONCEPTS LN THE KIDNEY Gina Louise Sirianni A thesis submitted in confonnity with the requirements for the degree of Master of Science Graduate Department of Pharmacology, University of Toronto O Copyright by Gina Louise Sirianni ( 1997) National Library Bibliothêque nationale l*l of Canada du Canada Acquisitions and Acquisitions et Bibliographie Services services bibliographiques 395 Wellington Street 395. rue Wellington OttawaON KIA ON4 Ottawa ON KIA ON4 Canada Canada The author has granted a non- L'auteur a accordé une licence non exclusive licence allowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or seIl reproduire, prêter, distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/film, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fiom it Ni la thèse ni des extraits substantiels may be printed or othenvise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. To My Parents Clearance Concepts in the Kidney Gina Louise Sirianni (M.Sc.), 1997 Department of Pharmacology, University of Toronto (Abstract) The kidney is an important elirninating organ. capable of metabolism and excretion. The fractional excretion value (FE, unbound urinary clearance normalized to glomemlar filtration rate) is typically used to detemine whether a compound is net fdtered (FE = I).
    [Show full text]
  • Practical Aspects of Therapeutic Plasma Exchange (PLEX / TPE) for Neurologists
    Saturday, May 31st Symposium on Plasma Exchange for CNS Demyelinating Diseases 11:00 a.m. – 11:55 a.m. Practical Aspects of Therapeutic Plasma Exchange (PLEX / TPE) for Neurologists David M. Ward, MD, FRCP Professor, Division of Nephrology, University of California San Diego Medical Director, Therapeutic Apheresis Program Associate Medical Director, Kidney/Pancreas Transplantation Practical Aspects of Plasma Exchange for Neurologists DISCLOSURES: The speaker has the following potential conflicts . TerumoBCT, Inc. – Honoraria, Consulting . Therakos, Inc. – Honoraria . Alexion Pharmaceuticals – Advisory Board . Aethlon Medical Inc. – Consulting WARNING: OFF-LABEL USES Therapeutic plasma exchange (plasmapheresis) is widely acknowledged as standard treatment for many diseases. In the USA, the FDA has approved numerous devices for the performance of plasma exchange, but not for specific indications. Thus all specific indications are regarded as “off-label” uses. [email protected] 1 Practical Aspects of Plasma Exchange for Neurologists OUTLINE: . Types of therapeutic apheresis . Expanding utilization of apheresis therapies . Methods and technologies of plasma exchange (TPE / PLEX): • centrifugal • membrane . TPE / PLEX treatment options and prescription . Kinetics of removal of autoantibodies . Intensity and adequacy of plasma exchange therapy . Adverse events . Applications in neurology [email protected] Practical Aspects of Plasma Exchange for Neurologists . Plasma Exchange (“PLEX”) = Therapeutic Plasma Exchange (“TPE”) ~– Plasmapheresis (“PE”) . “Apheresis” derives from . Ancient Greek “” = “to remove forcibly” . different root than “phoresis”, as in “electrophoresis”. PLEX / TPE / PE is one type of Therapeutic Apheresis [email protected] 2 Therapeutic Plasma Exchange PLASMA REMOVAL WITH RETURN OF CORPUSCLES (PLASMAPHAERESIS) FIRST PAPER JOHN J. ABEL, L. G. ROWNTREE AND B. B. TURNER From the Pharmacological Laboratory of the Johns Hopkins University Received for publication, July 16, 1914 I.
    [Show full text]
  • An Aminoglycoside Has a Normal Elimination Half-Life of 107 Minutes in Young Adults
    Name: ____________________ UFID #: ______________________ PHA 5127 Second Exam Fall 2007 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Put all answers on the bubble sheet TOTAL _______/130 pts 1 Name: ____________________ UFID #: ______________________ Question Set I (True or False) (15 points) True (A) or False (B). On the bubble sheet mark A for true or B for false Mark whether the following statements as true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 80,000 L/h Looking at intrinsic clearance you can tell this is a high extraction drug. 1: T F The oral bioavailability of this drug will be larger than 80%. 2: T F Plasma protein binding will affect the oral bioavailability of this drug. 3: T F The hepatic clearance of this drug is 1333 L/min 4: T F Plasma protein binding will affect the hepatic clearance of this drug. 5: T F Drug B, known to induce enzymes also responsible for metabolism of Drug A, will significantly affect the clearance of Drug A if given together. 2 Name: ____________________ UFID #: ______________________ Question Set II (18 points) True (A) or False (B). On the bubble sheet mark A for true or B for false Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the a peak concentration of 0.18 μg is observed (Co). When given orally, the oral bioavailability is 99.9 %. Plasma Protein Binding is 50% (fu=0.5).
    [Show full text]
  • Lntrarenal Blood Flow Distribution in Canine Puppies
    Pediat. Res. 5: 335-344 (1971) cardiac physiological development output renal blood flow maturation renal cortical volume lntrarenal Blood Flow Distribution in Canine Puppies PEDRO A. JOSE[62), ALEXANDER G. LOGAN, LAWRENCE M. SLOTKOFF, LAWRENCE S. LILIENFIELD, PHILIP L. CALCAGNO, AND GILBERT M. EISNER[61i Departments of Pediatrics, Physiology and Biophysics, and Medicine, Georgetown University School of Medicine, Washington, D.C., USA Extract The present study was designed to examine the developmental changes in renal blood flow distribution in canine puppies utilizing the techniques of xenon-133 (133Xe) wash- out, anatomic measurements, and para-aminohippuric acid (PAH) clearances and ex- tractions. The distribution patterns determined by analysis of the xenon washout curves were confirmed by studies of the intrarenal distribution of injected radioactive microspheres. The mean total blood flow was 1.2 ml/g kidney/min at 6 weeks of age and rose progressively to the adult value of 3.5 ml/g kidney/min at 14-16 weeks of age. The mean Component I flow, 1.7 ml/g/min at 6 weeks, increased to 4.7 ml/g/min at 14-16 weeks of age. The increase in Component I flow was associated with an increase in PAH extraction ratio. The low renal blood flow observed in the puppy less than 6 weeks of age appears to be due in large part to a small cortical volume. Anatomically, the amount of cortex/medulla ratio was less in the puppy than in the adult, and this was supported by the relatively low cortical volume of distribution noted in the wash- out studies.
    [Show full text]
  • Changes in Renal Blood Flow and Possibly the Intrarenal Distribution of Blood During the Natriuresis Accompanying Saline Loading in the Dog
    Changes in Renal Blood Flow and Possibly the Intrarenal Distribution of Blood during the Natriuresis Accompanying Saline Loading in the Dog Laurence E. Earley, Robert M. Friedler J Clin Invest. 1965;44(6):929-941. https://doi.org/10.1172/JCI105210. Research Article Find the latest version: https://jci.me/105210/pdf Journal of Clinical Investigation Vol. 44, No. 6, 1965 Changes in Renal Blood Flow and Possibly the Intrarenal Distribution of Blood during the Natriuresis Accom- panying Saline Loading in the Dog * LAURENCE E. EARLEY t AND ROBERT M. FRIEDLER (From the Thorndike Memorial Laboratory, Second and Fourth [Harvard] Medical Services, Boston City Hospital, and the Department of Medicine, Harvard Medical School, Boston, Mass.) Several recent studies have provided evidence ing limb of Henle's loop, resulting in the delivery that the increased excretion of sodium associated of a larger volume of fluid of lower sodium con- with expansion of the extracellular volume may centration to the transport sites of the ascending result in part from factors other than an increase limb of the loop. The present studies were under- in the filtered load of sodium. In the dog receiving taken to determine if a relationship could be dem- a mineralocorticoid, the infusion of isotonic saline onstrated between changes in the tubular reabsorp- may be accompanied by increased excretion of so- tion of sodium and changes in renal blood flow. dium without a spontaneous increase in the filtered It was observed that the increased excretion of so- load of sodium (1, 2). During saline loading glo- dium during isotonic expansion of the extracellular merular filtration rate (and filtered sodium) may volume was uniformly associated with increased be reduced experimentally without abolishing the renal blood flow, independent of spontaneous saline-induced natriuresis (1, 3-6).
    [Show full text]