Sulfatroxazole: pharmacokinetics, metabolism and urinary excretion in goats and pigs

Kinabo, L. D. B.; Nielsen, Poul

doi:10.1111/j.1365-2885.1986.tb00012.x

Cited by 5 publications

(4 citation statements)

References 12 publications

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“…In ruminants, the plasma protein binding of STZ and N4-STZ are about SO%, which is similar to the reported values for humans, goats, and pigs (Kinabo & Nielsen, 1986;Vree et al, 1986). The plasma protein binding of 5-OH-STZ, which is less, is similar to the reported values for humans (Vree et al, 1986;Vree & Hekster, 1987a).…”

Section: Discussionsupporting

confidence: 85%

“…Also in man (Vree et al, 1986) and in turtles (Vree et al, 1987c), methylation at the 4 position of the SMZ oxazoyl group greatly increases the susceptibility to hydroxylation, but in man the elimination half-life also increases three-fold from 9 h for SMZ to 26 h for STZ. Differences in STZ hydroxylation in several species (Kinabo & Nielsen, 1986;Vree et al, 1986;1987b,c;Vree & Hekster, 1987) may be explained by the presence of different amounts and/or types of P-450 cytochrome isoenzymes for hydroxylation in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…In goats, STZ was excreted mainly as the parent drug; the N4-acetyl and 5-hydroxy derivatives accounted, respectively, for only 19 and 18% (Kinabo & Nielsen, 1986). In pigs, dogs and snails STZ is slightly hyroxylated, but in turtles the hydroxylation pathway is dominant (Kinabo & Nielsen, 1986;Vree & Hekster, 1985;Vree et al, 1987b,c). The aim of this study in new-born and adult ruminants was to clarify the plasma (and milk) disposition, the metabolic pattern, the acetylation-deacetylation equilibrium, the protein binding, and the renal clearance of sulphatroxazole as well as the renal clearance of its N4-acetyl and 5-hydroxy metabolites.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics, metabolism and renal clearance of sulphatroxazole in calves and cows

Nouws¹,

Vree

Mevius³

et al. 1989

J Vet Pharmacol Ther

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The pharmacokinetic analysis of plasma concentration--time curves after a single i.v. dose of 20 mg/kg sulphatroxazole (STZ) to calves and cows revealed a small distribution volume of STZ (mean VD(area) = 0.22-0.26 l/kg) and an age dependent elimination (mean t1/2 6.6-18.8 h). In calves and cows, STZ was extensively metabolized into the N4-acetyl and 5-hydroxy derivatives. In the plasma of calves, the N4-acetyl metabolite (N4-STZ) was present in greater amounts than the hydroxy metabolite (5-OH-STZ), while in cows' plasma concentration of these two metabolites were similar. In the milk of dairy cows STZ concentrations paralleled those of the metabolites and were approximately 21 times lower than corresponding plasma concentrations. The mean plasma protein binding of STZ and its metabolites ranged from 36.4 to 82.5% of total concentration. The N4-STZ derivative was excreted by tubular secretion; the 5-OH-STZ and the parent compound, mainly by glomerular filtration. In calves the majority of STZ administered was excreted as N4-STZ (40-52%), while in cows the parent drug dominated the urinary excretion (36%).

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics, metabolism and renal clearance of sulphatroxazole in calves and cows

Nouws¹,

Vree

Mevius³

et al. 1989

J Vet Pharmacol Ther

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“…In pigs, the main metabolic pathway for most sulfonamides is supposed to be N-acetylation (Vree et al, 1985a;Kinabo & Nielsen, 1986;Rehm et al, 1986;Nouws et al, 1989Nouws et al, , 1991Shimoda et al, 1990)). The rate and extent of the in vivo acetylation of sulfonamides is dependent on the structure of the sulfonamide.…”

mentioning

confidence: 99%

The biotransformation of sulfadimethoxine, sulfadimidine, sulfamethoxazole, trimethoprim and aditoprim by primary cultures of pig hepatocytes

Mengelers¹,

Kleter²,

Hoogenboom³

et al. 1997

Vet Pharm & Therapeutics

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The in vitro biotransformation of three sulfonamides, trimethoprim and aditoprim, was studied using primary cultures of pig hepatocytes. Incubation of monolayer cultures with sulfadimethoxine (SDM), sulfamethoxazole (SMX) and 14C-sulfadimidine (SDD) resulted in the formation of the corresponding N4-acetylsulfonamide to different extents, depending upon the molecular structure of the drug. Addition of the acetylsulfonamides to the cells showed that these compounds were deacetylated, each to a different extent. A relatively low degree of acetylation (in the case of SDD) was paralleled by extensive deacetylation (i.e. AcSDD), whereas extensive acetylation (i.e. SMX) was in concert with minor deacetylation (i.e. AcSMX). The addition of bovine serum albumin to the medium resulted in a decrease in conversion of sulfonamides as well as acetylsulfonamides. The main metabolic pathway of 14C-trimethoprim (TMP) was O-demethylation with subsequent conjugation. Two hydroxy (demethyl) metabolites were formed, namely 3'- and 4'-demethyl trimethoprim, which were both glucuronidated while 3'-demethyl trimethoprim was also conjugated with sulphate. The capacity to form conjugates with either glucuronic acid or sulphate was at least as high as the capacity for O-demethylation since more than 90% of the metabolites were excreted as conjugates in the urine of pigs. Addition of 14C-aditoprim (ADP) to the hepatocytes led to the N-demethylation of ADP to mono-methyl-ADP and didesmethyl-ADP. During the incubation another three unknown ADP metabolites were formed. In contrast to TMP, no hydroxy metabolites or conjugated metabolites of aditoprim were formed. These in vitro results were in agreement with the in vivo biotransformation pattern of the studied sulfonamides and trimethoprim in pigs.

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Rapid chiral separation of metoprolol in plasma—application to the pharmacokinetics/pharmacodynamics of metoprolol enantiomers in the conscious goat

Leloux¹

1992

Biomedical Chromatography

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The plasma concentrations of metoprolol enantiomers have been determined by means of a direct phenyl carbamate-cellulose-based chiral high performance liquid chromatography assay using fluorimetric detection. This assay has been used to investigate the pharmacokinetics and pharmacodynamics of metoprolol enantiomers in the conscious goat. There is evidence that the pharmacokinetics of metoprolol in the goat occurs stereoselectively and that enantiomer-enantiomer pharmacokinetic interactions occur. R-Metoprolol is less effective in reducing the mean arterial blood pressure than S- and R/S-metoprolol.

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Sulfatroxazole: pharmacokinetics, metabolism and urinary excretion in goats and pigs

Cited by 5 publications

References 12 publications

Pharmacokinetics, metabolism and renal clearance of sulphatroxazole in calves and cows

Pharmacokinetics, metabolism and renal clearance of sulphatroxazole in calves and cows

The biotransformation of sulfadimethoxine, sulfadimidine, sulfamethoxazole, trimethoprim and aditoprim by primary cultures of pig hepatocytes

Rapid chiral separation of metoprolol in plasma—application to the pharmacokinetics/pharmacodynamics of metoprolol enantiomers in the conscious goat

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