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Biomedical subjects

T R Bates

Publications and source records attributed to T R Bates.

At least 19 recordsLinked to original sources
PubMed1979

Relative systemic availability of sulfapyridine from commercial enteric-coated and uncoated sulfasalazine tablets.

The absorption of sulfapyridine after a single 2.0-Gm oral dose of sulfasalazine, the drug of choice in the treatment of inflammatory bowel disease, as commercial uncoated and enteric-coated and uncoated tablets was evaluated in four healthy male adults. The peak plasma concentration of sulfapyridine after the enteric-coated tablets occurred at 20 hours on the average (compared to 14 hours for the uncoated tablets) and was only 50% of that attained from the uncoated tablets (P less than 0.05). The low relative extent of systemic availability of sulfapyridine from the enteric-coated tablets (65.5 +/- 6.3 per cent, mean +/- S.E.) compared to uncoated tablets may be due to absorption rate-dependent presystemic metabolism, since the relative extent of sulfapyridine absorption was 92.7 +/- 6.2 per cent compared to uncoated tablets. These findings suggest that enteric-coated and uncoated tablets of sulfasalazine are not bioequivalent. It remains to be determined whether the clinical efficacy of sulfasalazine from enteric-coated tablets is affected.

Adult↗
PubMed1979

Capacity-limited gut wall metabolism of 5-aminosalicylic acid, a therapeutically active metabolite of sulfasalazine, in rats.

The metabolic fate of 5-aminosalicylic acid (reported to be the active therapeutic moiety of sulfasalazine) was assessed in fasting rats as a function of dose (25-200 mg/kg) and administration route (oral, intraperitoneal, and intravenous). 5-Aminosalicylic acid is subject to both capacity-limited presystemic (apparently during first passage through the intestinal epithelium) and systemic acetylation. The possibility exists that 5-aminosalicylic acid also is acetylated presystemically after oral sulfasalazine administration to patients with inflammatory bowel disease. Any alteration in the absorption activity if N-acetyl-5-aminosalicylic acid is inactive or less active than 5-amino-salicylic acid.

Acetylation↗
PubMed1979

Apparent dose-dependent absorption of chlorothiazide in dogs.

The purpose of this study was to determine the effect of oral dose on the absorption of chlorothiazide in the dog. Chlorothiazide was quantitatively excreted in the urine after administration of 50-mg and 250-mg intravenous doses. In contrast, the urinary recovery of chlorothiazide after oral administration showed appreciable interanimal variation and decreased from 70.4% to 26.7% on the average as the oral dose was increased from 125 mg to 750 mg. Oral administration of a single 15-mg dose of propantheline bromide (a potent inhibitor of gastric emptying and intestinal motility) at--1 hr increased the absorption of a 250 mg oral dose of chlorothiazide in three out of four dogs. These results suggest that chlorothiazide absorption is dose dependent and apparently site specific.

Administration, Oral↗
PubMed1978

High-performance liquid chromatographic assay of sulfapyridine and acetylsulfapyridine in biological fluids.

A high-pressure liquid chromatographic method for the sensitive, rapid, and specific determination of sulfapyridine and its N-acetyl derivative in plasma and saliva was developed. A cyano-bonded, reversed-phase, high efficiency column was used. The system detected these sulfonamides in serum to 0.25 mg/liter and within only 6 min. Sulfapyridine was separated from its acetyl derivative with little interference from other drugs. The assay reproducibility was within 3%. The assay was highly useful for routine monitoring of patients receiving sulfasalazine for inflammatory bowel disease.

Acetylation↗
PubMed1977

Salivary excretion and pharmacokinetics of sulfapyridine after sulfasalazine.

The concentrations of sulfapyridine (SP) and N4-acetylsulfapyridine (AcSP) in the plasma and saliva of 5 healthy male adults (3 slow and 2 rapid acetylators) were determined as a function of time after a single 2.0-gm oral dose of sulfasalazine (salicylazosulfapyridine). SP absorption commenced 3.5 to 6 hr after sulfasalazine administration and occurred slowly (apparent absorption t1/2s ranged from 1.6 to 5 hr) irrespective of acetylator phenotype. Appreciable differences existed between slow and rapid acetylators with respect to the biologic t1/2 and total body clearance of SP. SP concentrations in the saliva correlated well with those in the plasma. The saliva:plasma concentration ratio for SP was 0.559 +/- 0.027 (mean of 5 subjects +/- SE) and was dependent of plasma concentration and saliva pH. The mean saliva:plasma concentration ratio for AcSP was lower (0.246 +/- 0.056), consistent with the pH-partition hypothesis, and showed considerably more intrasubject and intersubject variation than the ratio for SP. These findings suggest that measurement of SP concentrations in the saliva may be a convenient, noninvasive method for monitoring indirectly the steady-state plasma (serum) concentrations of SP in patients with ulcerative colitis or Crohn's disease who are receiving sulfasalazine.

Acetylation↗
PubMed1977

Gastrointestinal absorption of griseofulvin from corn oil-in-water emulsions: effect of amount of corn oil ingested in man.

The effect of the amount of emulsified corn oil ingested on the gastrointestinal absorption of griseofulvin in man was assessed after oral administration of 5, 10, 15, or 30 gm doses of a corn oil (40% w/w)-in-water emulsion dosage form, each containing 250 mg of microsize griseofulvin. For comparison, griseofulvin absorption from two-125 mg commercial tablets of ultramicrosize drug dispersed in polyethylene glycol 6;000 was also determined. Griseofulvin was almost completely absorbed from the microsize drug emulsions and ultramicrosize drug tablets, whereas 50% of an oral dose is absorbed from commercial microsize griseofulvin tablets. Only 4 gm of emulsified corn oil (as a 10-gm dose of emulsion) is required to maximize the uniformity and extent of griseofulvin absorptions. The emulsion dosage form is uniquely suited for pediatric use.

Absorption↗
PubMed1976

The influence of food on nitrofurantoin bioavailability.

The effect of food on the absorption of five commercial dosage forms of nitrofurantoin varying widely in drug release and dissolution characteristics was assessed in man after oral administration. Four healthy fasting and nonfasting male subjects received, in a crossover fashion, a single 100-mg dose of microcrystalline nitrofurantoin as an aqueous suspension, three different compressed tablets, and a single 100-mg dose of macrocrystalline nitrofurantoin in a capsule. Both the absorption and the duration of therapeutic urinary concentrations of nitrofurantoin were significantly increased after administration of the five products to nonfasting subjects. The enhancement in the bioavailability of the drug in the presence of food ranged from 20% to 400%, with the greatest absorption-enhancing effect occurring with those dosage forms exhibiting the poorest dissolution characteristics. It is concluded that single-dose comparative bioavailability studies of drug products normally administered with food should be performed in both nonfasting and fasting subjects.

Adult↗
PubMed1976

Warfarin.

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Biological Availability↗
PubMed1976

Cholestyramine-induced inhibition of salicylazosulfapyridine (sulfasalazine) metabolism by rat intestinal microflora.

The effect of multiple oral administration of the hypocholesterolemic agent cholestyramine (a strongly basic anion-exchange resin) on the metabolism of salicylazosulfapyridine by microflora present in the colon and cecum was assessed in conventional rats by following the time course of salicylazosulfapyridine and its metabolites in the urine and feces. The intestinal metabolism of salicylazosulfapyridine (a single 100 mg/kg oral dose), which involves reduction of the azo linkage by bacterial azo reductases and the liberation of sulfapyridine and 5-aminosalicylic acid (potential active metabolites of the drug), was markedly inhibited by the resin (250 mg/kg oral doses at -2, +2 and +6 hours), resulting in an enhanced fecal excretion of intact salicylazosulfapyridine. The existence of a rank-order correlation between the in vitro binding of salicylazosulfapyridine, sulfapyridine and 5-aminosalicylic acid to the resin and their fecal excretion pattern in resin-treated animals suggests that a direct cholestyramine-salicylazosulfapyridine interaction occurred within the intestinal tract and that in the bound state, the azo bond of the drug was inaccessible to bacterial azo reductases. These findings suggest that chronic oral administration of cholestyramine to patients with ulcerative colitis who are receiving salicylazosulfapyridine could result in a significant reduction in the absorption and metabolism of the drug and hence, in its therapeutic efficacy.

Aminosalicylic Acids↗
PubMed1976

Time course of free and N4-acetylated sulfapyridine concentrations in the plasma and saliva of man after sulfasalazine (salicylazosulfapyridine) administration: preliminary findings.

The time course of free and N4-acetylated sulfapyridine (SP) concentrations in the saliva and whole plasma was determined in a healthy male volunteer after a single 2.0 g oral dose of salicylazosulfapyridine (SASP) as four-500 mg commercial, uncoated tablets. The mean (+/- S.D.) plasma: saliva concentration ratios for free and acetylated SP was 2.04 (+/- 0.24) and 3.12 (+/-0.43), respectively, and were independent of plasma concentration and saliva pH. The elimination half-lives of SP and N4-acetyl SP could be determined from either salivary or plasma concentration-time data. These preliminary results suggest that measurement of saliva concentrations of free and acetylated SP may be a convenient, noninvasive method for monitoring indirectly the plasma concentrations of SP and acetyl SP in patients treated with SASP and for determining acetylator phenotype.

Acetates↗
PubMed1975

Bioavailability of micronized griseofulvin from corn oil-in-water emulsion, aqueous suspension, and commercial tablet dosage forms in humans.

The purposes of this investigation were to determine and to compare the oral absorption characteristics of micronized griseofulvin (500 mg) after its administration to humans in the form of a corn oil-in-water emulsion containing dispersed drug, an aqueous suspension, and two different commercial tablets (A and B). The four dosage forms were administered in a random crossover fashion to five fasting subjects, and drug absorption was assessed from urinary excretion data for the major metabolite of the antibiotic (6-desmethylgriseofulvin). The drug was most rapidly, uniformly, and completely absorbed from the corn oil-in-water emulsion. As compared to either the aqueous suspension, Tablet A, or Tablet B, three- to fourfold increases in the maximum body levels and a twofold enhancement in the bioavailability of the antibiotic were observed after administration of the emulsion dosage form. A mechanism based on the ability of the linoleic and oleic acids liberated during the digestion of corn oil to inhibit GI motility and stimulate gallbladder evacuation may explain the marked enhancing effect of emulsified corn oil on griseofulvin absorption in humans. This new lipid-in-water emulsion dosage form of micronized griseofulvin appears to offer several clinical advantages in the treatment of fungal infections.

Adult↗
PubMed1975

Apparent absorption kinetics of micronized griseofulvin after its oral administration on single- and multiple-dose regimens to rats as a corn oil-in-water emulsion and aqueous suspension.

This investigation was designed to quantitate and compare in the rat the oral absorption characteristics of micronized griseofulvin from a corn oil-in-water emulsion dosage form containing suspended drug and a control aqueous suspension after single-dose (50 mg/kg) and multiple-dose (50 mg/kg every 12 hr for five doses) administrations. The time course of intact drug in the plasma of all animals was best described by a one-compartment open model with apparent zero-order absorption. In contrast to that observed with the aqueous suspension, the onset of drug absorption after single-dose administration of the corn oil emulsion was significantly delayed. This difference disappeared upon multiple dosing of the two dosage forms, with the mean onset being quite rapid in both cases. Administration of a single dose of the antibiotic as the corn oil emulsion resulted in considerable increases in the maximum plasma levels of griseofulvin and in the duration, relative extent, and uniformity of drug absorption compared to those observed after administration of the control aqueous suspension. The potentiating effects of the lipid on drug absorption persisted on multiple dosing but at a somewhat reduced level.

Administration, Oral↗
PubMed1975

The effect of natural and surgically constructed aortopulmonary shunts on hemodynamic function in tetralogy of Fallot.

A hemodynamic model has been developed for the patient with tetralogy of Fallot. Equations representing the circulatory flow pattern and oxygen balance in this disease were incorporated into a computer program. With the computer model it is possible to simulate the effect of natural and surgically constructed aortopulmonary shunt flow on hemodynamic function in tetralogy of Fallot. Graphic representations of the computer output are presented which show how aortopulmonary shunt flow influences the physiology of exercise and hypoxic episodes. An explanation is advanced for the lack of correlation between resting arterial oxygen saturation and the incidence of hypoxic episodes. The model demonstrates the effect of surgical aortopulmonary shunts in eliminating hypoxic spells.

Aorta↗
PubMed1975

Nitrofurantoin.

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Biological Availability↗