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Pharmacokinetics 1831 plasma-drug concentrations and reductions in dosage as PharmacopoeialPreparations appropriate. Pharmacokinetics BP 2014: Cimetidine Injection; Cimetidine Oral Solution; Famotidine, nizatidine, and ranitidine do not inhibit Cimetidine is readily absorbed from the gastrointestinal Cimetidine Oral Suspension; Cimetidine Tablets; cytochrome P450, and the potential for drug interactions is tract and peak plasma concentrations occur after about an USP 36: Cimetidine in Sodium Chloride Injection; Cimetidine therefore reduced. hour when given on an empty stomach; a second peak may Injection; Cimetidine Tablets. 1. Penston J, Wormsley KG. Adverse reactions and interactions with H2- be seen after about 3 hours. Food delays the rate and may receptor antagonists. Med Toxicol l9B6; i: 192-2 16. slightly decrease the extent of absorption, with the peak 2. Somogyi A, Muirhead M. Pharmacokinetic interactions of cimetidine plasma concentration occurring after about 2 hours. 1987. Clin Phannacokinet 1987; 12: 321-66. 3. Smith SR, Kendall l\U. Ranitidine versus dmetidine: a comparison of The bioavailability of cimetidine after oral doses is about their potential to cause clinically important drug interactions. Clin 60 to 70%, due to hepatic first-pass metabolism. Cimetidine Phannacokinet 1988; 15: 44-56. is widely distributed and has a volume of distribution of 4. Shinn AF. Clinical relevance of cirnetidine drug interactions. Drug Safety about I litre/kg and is weakly bound, about 20%, to plasma 1992; 7: 245-67. proteins. The elimination half -life from plasma is about 2 Alcohol. hours and is increased in renal and hepatic impairment. Any interaction between H,-antagonists and Cimetidine is partially metabolised in the liver to the alcohol is generally thought unlikely to be clinically signif­ sulfoxide and to hydroxymethylcimetidine. About 50% of 1735.2). icant (see p. an oral dose, and 75% of an intravenous dose, is excreted unchanged in the urine in 24 hours. After an oral or Antacids. Single-dose studies of the interaction between parenteral dose of 300 mg, blood concentrations remain dmetidine famotidine, or ranitidine and antacids 1 have above that required to provide 80% inhibition of basal generally shown a reduced bioavailability of H,-antago­ gastric acid secretion for 4 to 5 hours. Cimetidine crosses the nist. The neutralising capacity of the antacid appears to be placental barrier and is distributed into breast milk. a factor in determining whether an interaction occurs and Cimetropium bromide is a quaternary ammonium a dose with less than 50 mmol neutralising capacity will Reviews. have little, if any, effect on H,-antagonist absorption. l. Somogyi A, Gugler R. Clinical pharmacokinetics of cimetidine. Clin antimuscarinic with peripheral effects similar to those of 8: Smaller doses of antacid taken separately from the H,­ Phannacokinet I 983; 463-95. atropine (p. 1312.1 ) . It has been used as an antispasmodic in 2. Lin JH. Pharmacokinetic and pharmacodynamic properties of histamine antagonist should reduce the impact of this interaction, the treatment of gastrointestinal disorders, in usual doses of Hrreceptor antagonists: relationship between intrinsic potency and 50 and there are some data to suggest that absorption is not effective plasma concentrations. Clin Phannacokinet 1991; 20: 218-36. mg two or three times daily orally or by rectal as greatly affected with concomitant longer· term use. 3. Gladziwa U, Klotz U. Pharmacokinetics and pharmacodynamics of Hr suppository. It has also been given intramuscularly or receptor antagonists in patients with renal insufficiency. Clin 1. Gugler R, Allgayer H. Effects of antacids on the clinical pharmacokinetics intravenously in usual doses of 5 mg. Phannacokinet 1993; 24: 319-32. of drugs: an update. Clin Pharmacakinet 1 990; 18: 210-19. I. Dobrilla G, et a!. Longterm treatment of irritable bowel syndrome with Antifungals. Itracanazole increased the area under the con­ Children. Renal function is limited in the first few months cimetropium bromide: a double blind placebo controlled clinical trial. 31: centration-time curve of cimetidine, and reduced the total of life and half-lives of 1.1 to 3.7 hours have been Gut 1990; 355-8. 2. Marzio L, et at. Effect of cimetropium bromide on esophageal motility plasma clearance and renal tubular secretory clearance of reported for cimetidine in neonates; 1·3 less frequent dosing and transit in patients affected by primary achalasia. Dig Dis Sci 1994; 39: cimetidine in a pharmacokinetic study in 8 healthy sub­ may therefore be required for preterm neonates and those 1389-94. jects.1 The authors proposed that this was due to inhibi­ with renal impairrnent.1 3. Savino P, et al. Cimetropium bromide in the treat:rllent of crisis in Pediatr Gastraenterol Nutr 2002; 34: 417-9. tion of P-glycoprotein-mediated renal tubular secretion. In older infants and children maturation of renal infantile colic. 1 1. Karyekar CS, et at. Renal interaction between itraconazole and function is complete and the clearance of cimetidine is cirnetidine. 1 Clin Pharmacal 2004; 44: 919-27. increased compared with that in adults; younger children show higher clearance values than older children 4 ProprietaryPreparations (details are given in Volume B) Antihistamines. Cimetidine may increase the serum con­ For details of doses used in children, see Administration centration of hydroxyzine, see p. 631.2. in Children, p. 1827.3. Single-ingredient Preparations. Ita!.: Alginor. 1. Ziemniak JA, et a!. The pharmacokinetics and metabolism of dmetidine Antimuscarinics. The antimuscarinic prapantheline delays in neonates. Dev Phannacol Ther I 984; 7: 30-8. 2. eta!. gastric emptying and reduces intestinal motility and has Lloyd CW, The pharmacokinetics of cimetidine and metabolites in a neonate. Drug Intell Clin Pharm 1985; 19: 203-5. been reported to reduce the bioavailability of cimetidine 1 3. Stile IL, et al. Pharroacokinetic evaluation of dmetidine in newborn 1. Kanto J, et at. The effect of metoclopramide and propantheline on the infants. Clin Ther 1985; 7: 361-4. gastrointestinal absorption of cimetidine. Br 1 Clin Pharmacal 1981; ll: 4. Somogyi A. et at. Cimetidine pharmacokinetics and dosage requirements 629-3 1. in children. Eur .JPediatr 1985; 144: 72-6. Histamine.For the effect of cimetidine on histamine given Preparations exogenously, see p. 2525.3. ..... ....., ......... .. ... ...................... ProprietaryPreparations (details are given in Volume B) Melatonin.For the effect of cimetidine on melatonin, see p. 2552.2. Single·ingredient Preparations. Arg. : Ulcerfen; Austral.: Cime· hexalt; Magicul; Tagamet; Austria: Cimetagt; Neutromed; Neutronorm; Sodexx Cimetidinet; Ulcometint; Ulcostad; Belg. : Cinitapride is a substituted benzamide used for its prokinetic Probenecid. Probenecid reduced the clearance of both Doccimetit; Nuardin; Braz.: Cigametet; Cimedax; Cimetidan; properties. It is given as the acid tartrate in oral doses of l mg cimetidine1 and famotidine2 in small studies in healthy Cimetilab; Cimetinax; Cimetival; Cintag; Cintidina; Etidine; three times daily before meals in the management of subjects. It was suggested that probenecid inhibited renal Pristonal; Prometidine; Tagaliv; Tagamet; Ulcedine; Ulcenon; gastroparesis and gastro-oesophageal reflux disease tubular secretion, although it was felt that the interaction Ulceract; Ulcimet; Ulcinax; Ulcitrat; Canad. : Novo·Cimetine; (p. 1807.2). was unlikely to be clinically significant.1 Nu-Cimet; China: ALi Wei (''!:\Lilt);Changfu YouShu (i\:';l;{:lt 1. Gisdon LG, et a!. The effect of probenecid on the renal elimination of :If); Hai Fu Xin (il!f'i*Jt); Nuo Mei Shu (iff'li'::lf);Tagamet (� cimetidine. Clin Pharmacal Ther 1989; 45: 444-52. i I'!�); Tang Feng Xiweining Ying Qu Preparat ons . (ii!f$); (i't\cJ1.'T'); (:;lii!ll); ........ ........ ........... ......... ......... .... ... .. .................... .............. ..... ,. 2. Inotsume N, et al. The inhibitory effect of probenecid on renal excretion You Ni Ding (::ltilOT); Cz. : Primamett; Fr.: Stomedine; of famotidine in young, healthy volunteers . .J Clin Phannaco/ 1990; 30: ProprietaryPreparations (details are given in Volume B} 50-6. Tagamett; Ger.: Cimebetat; Cimehexalt; CimLicht; H 2 Block­ er; Gr. : Alkastom; Besidin; Campanex; Cimeton; Gastrolene; Single·ingredient Preparations.Arg. : Cinigest; Paxapride; Rogas� Grinolon; Haldin; Ipirovet; Medelan; Metracine; Oskoval; Pallo· tril; Mex. : Binitab; Pemix; Spain: Blaston; Cidine. Prokinetic drugs. Metaclopramide may reduce the bioavail­ sixanet; Piovalen; Sasapir; Tagamet; Tamper; Tanapas; Thera· ability of cimetidine possibly due to reduction of gastroin Mex. : Pridamiral Pack. � pekin; Tinder; Trisolvenol; Ulcogranil; Hong Kong: Cementin; Multi-ingredient Preparations. testinal transit time.1·3 A similar interaction has been Cimedinet; Cimeta; Citidine; Gastabt; Gastidinet; Magicult; reported between tbe prokinetic drug cisapride and both Maritidinet; Sirnaglen; Syncomett; Tagamet; Timett; Ulcerin; cimetidine4 and ranitidine.5 The clinical significance of this Ulcomet; India: Cimetin; Lock·2; Indon.: Cimexol; Corsamet; Cisapride (BAN, USAN, r!NN) interaction is questionable since such combinations may Licomet; Nulcer; Sanmetidin; Tagamett; Ulcedinet; Ulcumet; be clinically effective, although the use of cisapride is now Ulcusant; Ulsikur; Xepamet; Irl. : Cedinet; Cimagent; Cirnel· Cisaprid;. Cisap/i\Ja; CiSi\ptklas; Ci?<fprid�. mongt!Jy�rat&; restricted in many countries. For the effect of
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