Bioavailability of sulfamethoxypyridazine following intramuscular or subcutaneous administration in goats Sk Garg, Rp Uppal
To cite this version:
Sk Garg, Rp Uppal. Bioavailability of sulfamethoxypyridazine following intramuscular or subcu- taneous administration in goats. Veterinary Research, BioMed Central, 1997, 28 (1), pp.101-104. hal-00902463
HAL Id: hal-00902463 https://hal.archives-ouvertes.fr/hal-00902463 Submitted on 1 Jan 1997
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Bioavailability of sulfamethoxypyridazine following intramuscular or subcutaneous administration in goats
SK Garg RP Uppal2
t Deparimew of Pharmacology and Toxicology, College of Veterinary and Animal Sciences, HP Agricultural University, Palampur, 176 062; 2 CCS Harvana Agricultural University, Hisar, l25 004, India
(Received 20 February 1996; accepted l6 July 1996)
Summary ― The pharmacokinetics of sulfamethoxypyridazine (SMP) was investigated in goats after a single intramuscular (im) or subcutaneous (sc) administration ( 100 mg/kg body weight). The bio- logical half lives of SMP following im and sc administration were found to be 11.0 and 13.7 h, respectively. The systemic availabilities of the drug were calculated to be 68.6 and 58.7% following im and sc injections, respectively. The rapidity of absorption, almost similar availability, compara- tively longer biological half-life and ease of administration suggest that the sc route of administra- tion might be preferred over the im route. To achieve and maintain serum concentrations 25 pg/mL, a rational dosage regimen of SMP for goats would be 55 and 38 mg/kg body weight as the loading and maintenance doses, respectively, with a dosage interval of 24 h by the sc route. sulfamethoxypyridazine / pharmacokinetics / bioavailability / goat
Résumé ― Biodisponibilité de la sulfaméthoxypyridazine après administration intramusculaire ou sous-cutanée chez la chèvre. La pharmacocinétique de la sulfaméthoxypyridazine (SMP) a été étudiée chez des chèvres après une administration intramusculaire (IM) ou sous-cutanée (SC) unique (100 mg/kg poids corporel). Les demi-vies biologiques de la SMP après administration IM et SC étaient de 1 et 13,7 heures, respectivement. Les disponibilités systémiques de la SMP étaient de 68,6 et 58,7 %, après injections IM et SC, respectivement. La rapidité d’absorption, une disponibilité peu différente, une demi-vie comparativement plus longue, et la facilité d’administration suggèrent que la voie SC peut être préférée à la voie IM. Afin d’obtenir une concentration sérique de 25 Ng/mL et de la maintenir, la première dose de SMP et les doses suivantes devraient être de 55 et 38 mg/kg de poids corporel, respectivement, avec un intervalle de 24 heures entre les injections. sulfaméthoxypyridazine / pharmacocinétique / biodisponibilité / chèvre
* Correspondence and reprints: Department of Pharmacology and Toxicology, College of Veterinary Science and Animal Husbandry, CS Azad University of Agriculture and Technology, Mathura Campus, Mathura 281 001, India. Tel: (91 ) 0565 403455; fax: (91 ) 0565 4048199 INTRODUCTION injected sc in the caudo-lateral aspect of the thigh region of the same animals. The sc dose and sam- Blood level and studies on pharmacokinetic pling times were the same as for the im injec- a sulfamethoxypyridazine (SMP), long-acting tion. Serum was separated and stored at -20 °C sulfonamide, in different species of animals, until analysis within 20 days of collection. namely calves and cattle (Faustini and Vaghi, The concentration of SMP in serum 1962a; Stewart and Paris, 1962; Silvestri et al, samples was determined the 1967), sheep (Stewart and Paris, 1962; Linken- spectrophotometrically by method of Bratton and Marshall heimer and Stolzenberg, 1965b), buffalo calves (1939). (Sidhu and Srivastava, 1992), swine (Faustini The pharmacokinetic analysis of serum SMP and Vaghi, 1962b; Linkenheimer and Stolzen- concentration-time data for each goat was per- berg, 1965a) and dogs and horses (Stewart and formed with the aid of a non-linear iterative Paris, 1962) following intravenous (iv), intra- curve fitting computer program (Statis, Version peritoneal (ip) or oral routes of administration 3, M/s, Clydesoft, Glasgow, UK). The values have revealed significant interspecies variations of systemic availability (F (%)) following both in acetylation and pharmacokinetics. Data are im and sc routes were determined from standard available on the pharmacokinetics of a number equation (Baggot, 1977) by utilizing the mean of sulfonamides (Gogh, 1980; Shetty and Asuzu, values of AUC and (3 for iv route reported earlier 1989) including SMP in goats (Garg et a], 1994) (Garg et al, 1994).). following iv administration; however, pharma- By using the pharmacokinetic data generated cokinetic data or following intramuscular (im) in the present study, a suitable dosage regimen of subcutaneous (sc) administration are apparently SMP for goats was computed (Baggot, 1977).). lacking in most species, including goats.
The sc route of administration has been rec- RESULTS ommended for animals because of rapid absorp- tion, and ease of administration good availability The mean serum concentrations of SMP at dif- et al, 1988; Wilson et al, 1989; et (Jernigan Garg ferent time intervals after im and sc administra- a], 1995). The present study was undertaken, there- tion are presented in table I. Serum concentration fore, to the pharmacoki- investigate comparative >_ 25 pg/mL were achieved within 2.5 and netics of SMP in goats after im and sc adminis- 10 min after im and sc administration, respec- tration. Based on the results obtained, a suitable tively. The peak serum concentrations (Cniax) dosage regimen for goats will be recommended. of 190.6 ± 28.8 and 131.9 ± 4.9 pg/mL were observed at 2 and 4 h following drug adminis- MATERIALS AND METHODS tration by the im and sc routes, respectively. Thereafter, the drug concentrations in serum Four adult female Gaddi goats weighing between declined gradually, and therapeutic concentra- 12.5 and 19.5 kg were used. The animals were tions (25 pg/mL) were maintained for more than fed locally available green tree leaves, concen- 24 h as shown in table 1. trate and mineral water was mixture, and pro- The serum concentration-time data in the vided ad libitum. present study were fitted to a one-compartment Injectable SMP (25% solution; Aldazin, open model with two exponentials describing Alved Products, Madras, India) was adminis- the first-order absorption and elimination phases. tered im in the neck region to all the animals at a The correlation coefficient values (r) for the one dose of 100 mg/kg body weight. Blood samples compartment fit were 0.93 ± 0.02 and 0.97 ± (4 mL each) were drawn from the jugular vein at 0.006 for im and sc routes, respectively. The 2.5, 5, I 0, 20 and 40 min and 1, 1.5, 2, 4, 6, 8, 12, weighting mode for fitting the serum concen- 24, 48 and 72 h post injection. After an inter- tration-time curve was kept at zero. Various vening wash-out period of 21 days, SMP was pharmacokinetic determinants describing the absorption and elimination phases of SMP fol- lowing drug administration by either of the routes are presented in table II.
DISCUSSION
The data presented in table I revealed that fol- lowing extravascular administration of SMP, therapeutic concentrations were achieved within 2.5 to 10 min. SMP was rapidly absorbed as reflected by the early blood levels and absorption half-life values of 0.24 and 0.09 h for the im and sc routes, respectively. The elimination half-lives of SMP in goats after im and sc administration were l 1.0 and 13.7 h, respectively, which are markedly longer than the tp2p of this drug (6.28 h) following iv admin- istration (Garg et al, 1994). To our knowledge, no data is available on the tll2o values of sulfon- amides after im or sc administration in domestic animals including goats; therefore, it is not possi- ble to comment on the comparative pharmacoki- netics of SMP following im or sc administration. The systemic availabilities of SMP in goats Faustini R, Vaghi MA (1962a) Some pharmacologic following im and sc administration were very properties of sulfamethoxypyridazine and a new similar (table II). Therefore, taking into consid- sulfonamide, sulfapyrazinemethoxine in calves. Am J Vet Re.s 58-64 eration the rapidity of absorption, similar avail- 23, ability, comparatively longer biological half-life Faustini R, Vaghi MA (1962b) Blood levels of sulfa- methoxypyridazine, sulfapyrazinemethoxine and and ease of administration, the sc route be may sulfamethazine in swine. Am J Vet Res 23, 65-69 preferred over the im route. Based on the dis- Garg SK, Uppal RP, Riviere JE ( 1994) Serum disap- position kinetics of gentamicin, similar types of pearance and urinary excretion of sulfa- observations and recommendations have been methoxypyridazine in goats. Rev Elev Med Vet made for dogs (Wilson et al, 1989), cats (Jerni- !v.t7’ro!47,2)5-2)88 gan et al, 1988), and goats (Garg et al, 1995). Garg SK, Verma SP, Uppal RP ( 1995) Pharmacokinet- For most of the sulfonamides, the minimum ics of gentamicin following single-dose parenteral administration to Br VetJ 151, 454-458 inhibitory concentration (MIC) for a variety of goats. bacteria is in the range of 0.1 to 64 Ng/mL (Man- Gogh HV (1980) Pharmacokinetics of nine sulfon- del and Sande, 1985). Taking into consideration amides in goats. J Vet y/)6!rmam/ Ther 5, 69-811 a MIC of 25 pg/mL, which is known to be effec- Jemigan AD, Wilson RC, Hatch RL, Kempt DT (1988) Pharmacokinetics of after tive against most of the microorganisms (Nawaz, gentamicin intravenous, intramuscular and subcutaneous administration in 1980), a suitable dosage regimen for SMP was cats. Am J Vet Res 49, 32-35 computed by the formula: Linkenheimer WH, Stolzenberg SJ (1965a) Pharma- cology characteristics of four sulfonamides in swine. Am J Vet Res 26, 1086-1094 where D’ is the maintenance is the dose, CP(min) Linkenheimer WH, Stilzenberg SJ (19656) Pharma- MIC, Vd(area) is the value of apparent volume cologic characteristics of four sulfonamides in of distribution, (3 is the elimination rate constant sheep. Am J Vet Res 26, 1095-1 I 02 and i is the dosage interval; F is the systemic Mandel GL, Sande MA (1985) Sulfonamides, availability. Priming or loading dose was cal- trimethoprim, sulfainethoxazole and agent for uri- culated by omitting -1 from the above equation. nary tract infections. Goodnran and Gil»ra»’s the Using this equation, the loading and mainte- Pharmacological Basis o/ 7&dquo;/)fra)<’M