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At least 19 recordsLinked to original sources
PubMedDate not supplied

Sulfadimethoxine-bucolome interaction in rabbits: role of N4-acetylsulfadimethoxine, a major metabolite of sulfadimethoxine.

The role of N4-acetylsulfadimethoxine (N4-AcSDM), a major metabolite of sulfadimethoxine (SDM), in protein binding and pharmacokinetic interactions between SDM and bucolome (BCP) was investigated in rabbits. When SDM and BCP were intravenously co-administered, BCP indirectly reduced the serum protein binding of SDM by causing a marked increase of N4-AcSDM concentration in serum, and significantly increased the steady-state volume of distribution (Vss) and total body clearance (C1tot) of SDM. In addition, the co-administration of N4-AcSDM was found to increase Vss and C1tot of SDM. These results lead us to conclude that N4-AcSDM plays an important role in protein binding and pharmacokinetic interactions between SDM and BCP in rabbits. Several investigations have demonstrated that a metabolite plays an important role in drug-drug interaction. For example, Sellers et al. (1) reported that when warfarin and chloral hydrate are co-administered, a major metabolite of chloral hydrate, trichloroacetic acid, reduces the plasma protein binding of warfarin and enhances its anti-coagulant activity. Our previous paper (2) showed that probenecid indirectly reduces the plasma protein binding of sulfadimethoxine (SDM) by causing a marked increase in the plasma concentration of N4-acetylsulfadimethoxine (N4-AcSDM), which is a major metabolite of SDM (3) and strongly displaces SDM from its plasma protein binding sites (2). However, as yet the role of this metabolite in drug-drug interaction has not been fully examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Sulfadimethoxine as a promising drug in the treatment of infections caused by Mycobacterium kansasii and Mycobacterium xenopi--differentiation between M. kansasii and M. marinum and between M. gordonae and M. scrofulaceum by the susceptibility testing to sulfadimethoxine].

Susceptibility testing to sulfadimethoxine of various mycobacteria was made using Ogawa egg medium containing various concentrations of the drug. Each medium was inoculated by a 0.02 ml-sample of bacterial suspensions (10 mg wet weight per ml) prepared from 10 day-old (M. tuberculosis, 14 day-old) cultures growing on Ogawa egg medium after homogenizing the bacteria by shaking with glass beads. The media inoculated were incubated at 37 degrees C for 14 days (M. marinum, at 28 degrees C). The minimal inhibitory concentration (MIC) was determined as the lowest drug concentration on which the growth of bacteria was completely inhibited. However, residual growth occurred often. This was regarded as negative growth, because control medium containing no drug always exhibited abundant membraneous growth. Of the mycobacteria tested, M. kansasii (MICs, 0.8-3.2 micrograms/ml) and M. xenopi (MICs, 0.2-3.2 micrograms/ml) were most susceptible to this drug. Other mycobacteria showed the MICs higher than 3.2 micrograms/ml. The drug seemed to be useful in the treatment of infections caused by M. kansasii and M. xenopi. Furthermore, the susceptibility testing to sulfadimethoxine was considered to be useful for differentiation between two photochromogens, M. kansasii and M. marinum and for differentiation between two scotochromogens, M. scrofulaceum and M. gordonae (Fig. 3 and 4).

Humans↗
PubMed1981

Effect of sulfadimethoxine on thiopental distribution and elimination in rats.

The effect of sulfadimethoxine on the distribution and elimination of thiopental was examined by comparing the change in the steady-state volume of distribution (Vss) determined from both in vivo plasma elimination and in vitro serum and tissue binding studies in rats. The plasma disappearance of thiopental after a 12-mg/kg iv dose followed a biexponential decline in both the control and sulfadimethoxine-treated rats. The plasma thiopental concentrations under the steady-state plasma sulfadimethoxine concentration (500 micrograms/ml) were significantly lower than those of the control rats. In the sulfadimethoxine-treated rats, the pharmacokinetic parameter beta significantly decreased while Vss significantly increased to 3.6-fold that of the control rats. With sulfadimethoxine, a significant increase was observed in the apparent dissociation constant (Kd) of thiopental to serum protein by equilibrium dialysis, but the total number of binding sites was not altered. The in vitro serum free fraction of thiopental was increased to about 2.6-fold in the presence of sulfadimethoxine. The free fraction of thiopental in the main distribution tissues (liver, muscle, and adipose) was determined by equilibrium dialysis with and without sulfadimethoxine. No significant changes were observed in the presence of sulfadimethoxine. The calculated Vss, determined by the free fractions from in vitro binding experiments, also showed a significant increase. The ratio of Vss with sulfadimethoxine to that of the control rats was 2.8. The total clearance did not change, but the intrinsic clearance decreased to one-half of that of the control rats due to the increase of the serum free fraction by sulfadimethoxine. It was concluded that sulfadimethoxine caused a displacement of thiopental in plasma protein binding, which significantly increased the free fraction of thiopental, and this result may explain the significant increase of Vss and the decrease of both beta and intrinsic clearance. Tissue binding of thiopental, however, was unaffected by sulfadimethoxine.

Animals↗
PubMed2006

Degradation kinetics of manure-derived sulfadimethoxine in amended soil.

Spreading of contaminated manure into agricultural lands as fertilizer is one of the major routes through which veterinary antibiotics enter the environment. In this study, the degradation of manure-derived sulfadimethoxine, a widely used veterinary sulfonamide antibiotic, in manure-amended soil was investigated. A kinetic model, called the availability-adjusted first-order model based on the first-order kinetics and an assumption of the availability of target compound during the degradation process, was developed and was found to fit sulfadimethoxine degradation well. The effect of initial sulfadimethoxine concentration showed that the degradation rate constant increased with decreasing initial concentration, indicating that the bioactivity of the degrading microorganisms in manure-amended soil was sensitive to sulfadimethoxine concentration. Sulfadimethoxine degradation was accelerated with increasing manure content in amended soil. Degradation in nonamended soil was significantly slower than in manure-amended soil. This indicated that sulfadimethoxine may become more persistent once it reaches soil after leaching from manure and that storage of manure for a certain period before application is needed to diminish sulfadimethoxine contamination. Sulfadimethoxine degradation was effectively enhanced with increasing moisture of amended soil. No adverse effect was observed with manure storage on the degradation of manure-derived sulfadimethoxine in amended soil.

Kinetics↗
PubMed1988

Disposition of sulfadimethoxine in the lobster (Homarus americanus).

The long-acting sulfonamide antibacterial, sulfadimethoxine, has the potential for use in pen-held lobsters, Homarus americanus for treatment of gaffkemia. We evaluated the disposition of sulfadimethoxine after intrapericardial, oral or multiple oral administration of unlabelled or radiolabelled sulfadimethoxine (42 mg/kg) to 500 g lobsters. Elimination of parent sulfadimethoxine from hemolymph was very slow compared with elimination of the drug from blood of vertebrate species; the beta phase half-life was 77 hr in lobster as opposed to 7-40 hr in several vertebrate species. The pharmacokinetics of sulfadimethoxine after intrapericardial administration were linear up to 55 mg/kg, and binding of sulfadimethoxine to hemolymph proteins was constant over the range 14-200 micrograms/ml. During the first week after dosing, concentrations of sulfadimethoxine and metabolites (total radioactivity) were similar in all non-excretory tissues, such that muscle, shell and hemolymph contained the largest percentage of the administered dose. By 2 weeks and later, hepatopancreas and digestive tract contained the highest concentration and percentage of the dose, by total radioactivity. Part of the dose of sulfadimethoxine was excreted unchanged in urine and part was metabolized in hepatopancreas to unknown polar metabolites. The major vertebrate metabolite, N-acetylsulfadimethoxine, was a very minor metabolite in lobster. Although sulfadimethoxine was extensively metabolized in hepatopancreas, the polar metabolites were very slowly excreted, suggesting inefficient excretion mechanisms for elimination of polar xenobiotic metabolites in the lobster.

Animals↗
PubMed2006

Sulfadimethoxine degradation kinetics in manure as affected by initial concentration, moisture, and temperature.

Sulfadimethoxine is a widely used sulfonamide veterinary antibiotic and could be a source of agricultural contamination. Therefore, information is needed about its degradation kinetics in manure under aerobic conditions. Based on the analysis of first-order kinetics and the assumption that sulfadimethoxine availability for degradation in manure could be limiting, a new kinetic model was developed and was found to fit the degradation kinetics well. The degradation rate in sterile manure was found to be much lower than in nonsterile manure, indicating that biodegradation was significant. In biologically active manure, the degradation rate constant decreased with increasing initial concentration of sulfadimethoxine, implying that the activity of the degrading microorganisms was inhibited. Increasing moisture or temperature was found to increase sulfadimethoxine degradation in manure. Mixing manure containing high levels of sulfadimethoxine with manure containing lower levels may result in more rapid degradation, thus greatly diminishing sulfadimethoxine contamination in manure and significantly reducing sulfadimethoxine inputs into the environment. During treatment, keeping the manure moist and storing in a moderately warm place under aerobic conditions may also help to diminish sulfadimethoxine contamination.

Aerobiosis↗
PubMed2004

Pharmacokinetics of sulfadimethoxine and ormetoprim in a 5:1 ratio following intraperitoneal and oral administration, in the hybrid striped bass (Morone chrysops x Morone saxitalis).

Selected pharmacokinetic parameters for sulfadimethoxine and ormetoprim, administered in a 5:1 ratio, via the oral and intraperitoneal (i.p.) routes were determined in the hybrid striped bass (Morone chrysops x Morone saxitalis). Plasma concentrations of both drugs were determined by high-performance liquid chromatography. A first-order one-compartment model adequately described plasma drug disposition. The elimination half-lives for sulfadimethoxine following i.p. and oral administration were 26 and 10.5 h, respectively. The half-lives for ormetoprim administered via i.p. and oral routes were 7.5 and 3.9 h, respectively. Cmax for sulfadimethoxine via the i.p. and oral routes were calculated to be 27.7 (+/-9.0) microg/mL at 3.6 h and 3.2 (+/-1.2) microg/mL at 1.2 h, respectively. Cmax for ormetoprim via the i.p. route was calculated to be 1.2 (+/-0.5) microg/mL at 9.1 h and 1.58 (+/-0.7) microg/mL at 5.7 h for the oral route. The oral availability of sulfadimethoxine relative to the i.p. route was 4.6%, while the oral availability of ormetoprim relative to the i.p. route was 78.5%. Due to the nonconstant ratio of these drugs in the plasma of the animal, the actual drug ratio to use for determining minimum inhibitory concentration (MIC) is unclear. Using the ratio of the total amount of each drug that is absorbed as a surrogate for the mean actual ratio may be the best alternative to current methods. Using this ratio as determined in these studies, (2.14:1 sulfadimethoxine:ormetoprim) to determine the MICs the single 50 mg/kg oral dose of the 5:1 combination of sulfadimethoxine and ormetoprim appears to provide plasma concentrations high enough to inhibit the growth of Yersinia ruckeri, Edwardsiella tarda, and Escherichia coli.

Administration, Oral↗
PubMed1987

Compatibility of sulfadimethoxine and ormetoprim with lasalocid and monensin on performance of male broiler chickens.

We studied the effect of sulfadiomethoxine and ormetoprim (Rofenaid 40) in combination with lasalocid (Avatec) and monensin (Coban) on mortality, weight gain, and feed conversion of 2592 male broilers to 47 days of age. Four shuttle treatments were utilized: 1) monensin feeding for the entire trial; 2) sulfadimethoxine and ormetoprim feeding for the first 2 weeks, followed by lasalocid for the remainder of the trial; 3) sulfadimethoxine and ormetoprim feeding for the first 2 weeks, followed by monensin; and 4) sulfadimethoxine and ormetoprim feeding through week 3, then lasalocid for the remainder of the trial. No significant (P greater than .05) differences were observed in mortality among the four treatments. The combination of sulfadimethoxine and ormetoprim plus lasalocid significantly (P less than .01) improved weight gain and final body weight, but the length of time that sulfadimethoxine and ormetoprim were fed did not have any effect. Sulfadimethoxine and ormetoprim plus monensin treatment resulted in better feed conversion as compared with the other treatments.

Animals↗
PubMed1990

Ruminal excretion of sulfadimethoxine and sulfadimethyloxazole in goats and their influence on some enzyme activities and renal clearances.

Five clinically health goats were injected with sulfadimethoxine and sulfadimethyloxazole in a single dose of 100 mg/kg b. wt. by intravenous route. Highest concentration levels of sulfadimethoxine and sulfadimethyloxazole in rumen were detected 1 hour following intravenous injection, then the concentration for both compounds declined at 12 and 8 hours post administration, respectively. In addition, both types of sulfonamide completely disappeared in ruminal fluid samples taken after 24 and 12 hours, respectively. The rate of acetylation for sulfadimethoxine and sulfadimethyloxazole were nearly similar and occurred to a high extent in ruminal fluid (22.95 and 23.72%, respectively). On the other hand, both tested drugs increased significantly the ruminal gas production from the first to eight hours after i.v. injection in goats. Changes in the serum enzyme activities (SGOT, SGPT and alkaline phosphatase) observed with sulfadimethoxine and sulfadimethyloxazole, and represented by a significant decrease in the activity of SGOT and SGPT level, alkaline phosphatase 4 hours sulfadimethoxine and in GOT/GPT ratio 24 and 48 hours after i.v. injection, respectively. The creatinine clearance was significantly decreased after 4 hours following the i.v. administration of sulfadimethoxine and sulfadimethyloxazole in goats.

Alanine Transaminase↗
PubMed1977

Kinetics of drug-drug interactions in sheep: tolbutamide and sulfadimethoxine.

The interaction between sulfadimethoxine and tolbutamide in sheep involving displacement from protein binding sites was investigated quantitatively. A 52% increase in the unbound plasma concentration of tolbutamide was observed in vitro at 37 degrees after the addition of sulfadimethoxine (100 microgram/ml) to sheep plasma containing tolbutamide (50 microgram/ml). Transient changes in tolbutamide's unbound and total plasma concentrations were noted after acute intravenous administration of sulfadimethoxine to sheep receiving a constant intravenous infusion of tolbutamide. These observations were consistent with displacement of tolbutamide from plasma and tissue binding sites and redistribution of the displaced tolbutamide into body water spaces. The steady state of both agents featured little change in the total plasma tolbutamide concentration, a 150% increase in the unbound plasma tolbutamide concentration, and an inhibition of tolbutamide oxidation by sulfadimethoxine. A model is presented and mathematical relationships are derived that permit a quantitation of the interaction and that indicate the sulfadimethoxine's constant of metabolic inhibition (K1) for tolbutamide metabolism is 65 microgram/ml.

Animals↗
PubMed1990

Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfadimethoxine in man.

Sulfadimethoxine is metabolized by O-dealkylation, N4-acetylation and N1-glucuronidation. In man, only N1-glucuronidation and N4-acetylation takes place, leading to the final double conjugate N4-acetylsulfadimethoxine-N1-glucuronide. The N1-glucuronides are directly measured by high pressure liquid chromatography. When N4-acetylsulfadimethoxine is administered as parent drug, 30% of the dose is N1-glucuronidated and excreted. Fast acetylators show a shorter half-life for sulfadimethoxine than slow acetylators (27.8 +/- 4.2 h versus 36.3 +/- 5.4 h; P = 0.013), similarly the half-life of the N4-acetyl conjugate is also shorter in fast acetylators (41.3 +/- 5.2 h versus 53.5 +/- 8.5 h, P = 0.036). No measurable plasma concentrations of the N1-glucuronides from sulfadimethoxine are found in plasma. N1-glucuronidation results in a 75% decrease in protein binding of sulfadimethoxine. N4-acetylsulfadimethoxine and its N1-glucuronide showed the same high protein binding of 99%. Approximately 50-60% of the oral dose of sulfadimethoxine is excreted in the urine, leaving 40-50% for excretion into bile and faeces.

Acetylation↗
PubMed2003

Disposition of sulfadimethoxine in male llamas (Llama glama) after single intravenous and oral administrations.

This study determined the disposition of sulfadimethoxine in six, healthy, adult, gelded male llamas (Llama glama) by using a nonrandomized crossover design with i.v. dosing (58.8 +/- 3.0 mg/kg based on metabolic scaling) followed by oral dosing (59.3 mg/kg +/- 8.3). Blood samples were collected intermittently for a 72-hr period, and serum sulfadimethoxine concentrations were quantified using high-performance liquid chromatography. Serum sulfadimethoxine concentrations across time were subjected to standard pharmacokinetic analysis based on linear regression. Mean maximum serum concentration after oral dosing was 23.6 +/- 14.9 microg/ml, and extrapolated peak concentration after i.v. administration was 246.6 +/- 15.8 microg/ml. Total clearance of sulfadimethoxine was 45.4 +/- 13.9 L/kg. Half-lives after i.v. and oral administration were 541 +/- 111 min and 642.4 +/- 204.8 min, respectively. Oral bioavailability was 52.6 +/- 15%. These data suggest that the oral dose administered to llamas in this study, based on metabolic scaling from cattle, may be inadequate when compared with the reported minimum inhibitory concentration (512 microg/ml) breakpoint for sulfadimethoxine.

Administration, Oral↗