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Biomedical subjects

F L Tse

Publications and source records attributed to F L Tse.

At least 73 records · Page 4Linked to original sources
PubMed1982

The bioavailability of two commercial preparations of allopurinol tablets.

The relative bioavailability of two commercial preparations of 100 mg and 300 mg allopurinol tablets was examined in two groups of 16 healthy human subjects, one for each dosage level. Serum concentrations of allopurinol and its major metabolite, oxypurinol, were measured using a competitive protein-binding assay. After single doses of allopurinol, no significant differences between brands were revealed in the resultant serum levels of the drug or the metabolite, or in the relevant pharmacokinetic parameters. Serum oxypurinol levels were higher and more persistent than those of the parent drug. A comparison of the serum concentration profiles after 100 mg and 300 mg doses suggests that allopurinol absorption in humans may be dose dependent.

Absorption↗
PubMed1981

Effect of caffeine on circulating theophylline levels in beagle dogs.

The pharmacokinetic interactions of caffeine with theophylline were examined in two beagle dogs by administering 100 mg of aminophylline intravenously, 3 weeks before and immediately after repeated oral doses of caffeine. Serial plasma samples were analyzed for caffeine and theophylline simultaneously by high-performance liquid chromatography. Upon multiple oral dosing, 100 mg every 12 hr for 7 days, the caffeine half-life increased slightly in one dog but decreased in the other. As predicted from single-dose data, caffeine accumulation in plasma after repeated doses was slight, while plasma levels of the N-demethylated metabolite, theophylline, rose to about three times the initial values. After rapid intravenous doses of aminophylline, the theophylline half-life was 5-7 hr, which decreased slightly when the drug was administered concomitantly with caffeine during steady state of caffeine. The theophylline volume of distribution (0.75 liter/kg) was unaffected by caffeine. On the other hand, an acute aminophylline injection prolonged the elimination half-life and increased the apparent volume of distribution of caffeine, causing little overall change in its plasma clearance. The results suggested that interactions between theophylline and caffeine may be attributed to changes in drug distribution and drug elimination characteristics.

Aminophylline↗
PubMed1980

Bioavailability of propranolol in the dog.

The pharmacokinetics of propranolol in a fasted dog was examined following single oral, intraportal and intravenous doses. Extensive tissue uptake of propranolol occurred after intravenous dosing, the overall distribution volume was 11 liters/kg. Biological half-life was 1.5 hr, but was prolonged after oral and intraportal drug administration. Following oral doses, the absorption efficiency of propranolol as unchanged drug was 71%, while first-pass metabolism accounted for a further loss of 62% prior to its reaching the systemic circulation. Accordingly, the overall oral bioavailability was 27%.

Administration, Oral↗
PubMed1979

Pharmacokinetics of l-carnitine in man following intravenous infusion of dl-carnitine.

The pharmacokinetics of l-carnitine were studied in adult male patients following intravenous infusion of dl-carnitine hydrochloride-L-Carnitine appears to distribute into a rapidly perfused and then a more slowly perfused body space following administration. The overall apparent distribution volume Vd (ss) is consistent with extracellular body water. Serum levels of l-carnitine, from two different dose levels were adequately described by a two-compartment model. 80% of the administered dose was recovered in 24 hour post dose urine.

Adult↗
PubMed1977

Prednisolone bioavailability in the dog.

With a fasted dog as an animal model, the bioavailability and pharmacokinetics of prednisolone were studied following rapid intravenous injection and oral dosing of a prednisolone sodium phosphate solution and also following oral doses of prednisolone as tablets and a slurry. Hydrolysis of the phosphate ester to prednisolone in the body is extremely rapid and complete, thus permitting accurate calculation of the distribution volume of prednisolone. Enteral absorption of prednisolone from a slurry is superior to that from prednisolone tablets and from a prednisolone sodium phosphate solution. Reduced absorption from tablets, compared to the slurry, is probably due to tablet disintegration characteristics; reduced absorption from the solution is probably due to poor membrane permeability of the ionized drug. Information obtained from a single animal may indicate the need for expanded studies in humans.

Administration, Oral↗
PubMed1976

Propoxyphene and norpropoxyphene: influence of diet and fluid on plasma levels.

The influence of various test meals and ingested fluid volumes on the bioavailability and pharmacokinetics of propoxyphene and its major metabolite norporpoxyphene has been studied in healthy human subjects. The absorption of drug was delayed by all test meals, but the overall efficiency of absorption was either not affected or was slightly increased. Increased fluid volume intake decreased propoxyphene bioavailability. Plasma levels of metabolite correlated well with levels of unchanged drug, particularly in the first 2 hr after dosing, but were not markedly influenced by treatments.

Adult↗
PubMed1975

Treatment with sisomicin of complicated urinary tract infections in patients with varying degrees of renal function impairment, pharmacokinetics and dosage adjustment.

The efficacy, tolerance and pharmacokinetics of the new aminoglycoside antibiotic sisomicin, have been studied in 29 elderly male patients with varying degrees of renal function impairment and suffering from complicated urinary tract infections. The antibiotic was equally effective in patients with normal and impaired renal function and a cure (negative urine culture at one week follow-up) of 56% was obtained. There was little apparent toxicity with the dosage regimens used, although serum creatinine values were statistically but not clinically significantly increased in some patients following treatment. Serum half-lives of sisomicin were prolonged in cases of impaired renal function but accumulation of antibiotic could be prevented by varying dosing intervals between 8 and 24 hours based on serum creatinine values. There was good correlation between serum creatinine and sisomicin serum half-life values and a practical method is described for dose adjustment based on the relationship between serum half-lives and serum creatinine concentrations.

Aged↗
PubMed1975

Pharmacokinetics of minocycline in renal failure.

The pharmacokinetics of minocycline have been studied after single intravenous infusions and repeated oral doses to human subjects with varying degrees of renal impairment. There was no evidence of reduced drug clearance with reduced renal function after intravenous doses although there appeared to be an increase in the tissue distribution of antibiotic in the body in uremia. After identical multiple oral dosage regimens serum levels of antibiotic were comparable in normal and mildly uremic subjects. There was no evidence of renal toxicity in normal or uremic subjects with the repeated dosage regimen used.

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetics of acetylmethadols I: gas-liquid chromatographic determination of L-alpha-acetylmethadol and its major metabolites in plasma.

A gas chromatographic method is reported for simultaneously determining acetylmethadol, noracetylmethadol, and dinoracetylmethadol in plasma. Minimum detectable concentrations are 10 ng ml-1 for acetylmethadol using a flame ionization detector, and 5 and 25 ng ml-1 for noracetylmethadol and dinoracetylmethadol respectively using electron capture detection. Extraction efficiency is quantitative for acetylmethadol but lower for the metabolites. The method is useful for monitoring drug levels following therapeutic doses of acetylmethadol.

Chromatography, Gas↗
PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of bromocriptine in the rat.

The absorption, distribution, and excretion of bromocriptine were studied following oral and parenteral administration of non-radioactive and 14C-labelled drug in the rat. Total radioactivity was measured in blood, tissues, and excreta by liquid scintillation counting while the parent drug was determined in plasma and selected tissues by radioimmunoassay. The pharmacokinetic observations were compared with the time course of drug-induced hypothermia in cold-room acclimatized rats. The results indicated that oral doses of bromocriptine were rapidly, though incompletely (32-40 per cent), absorbed, but underwent extensive first-pass metabolism, resulting in an absolute bioavailability of only 6 per cent. The bioavailability increased to approximately 22 per cent in rats pretreated with the hepatic microsome inhibitor proadifen, thus suggesting the liver as the principal site of biotransformation. Absorbed bromocriptine showed preferential distribution into the tissues, although no apparent accumulation of drug-related material occurred in the body. The drug was eliminated almost exclusively by metabolism and biliary excretion into the faeces. Comparison of the pharmacodynamic and the pharmacokinetic profiles indicated a dose relationship between hypothermia and plasma bromocriptine concentrations but not total radioactivity levels. The hypothermic response was also intensified by proadifen pretreatment, thus confirming the parent drug as the pharmacologically active entity. It is believed that the previously reported delay in the onset of bromocriptine activity is not pharmacokinetic in nature, but is related to the properties of the receptors at the target site or to the pharmacologic events that result in the observed effects.

Animals↗
PubMedDate not supplied

Disposition of a silicon-containing amide, an inhibitor of acyl-CoA: cholesterol acyltransferase, in dog and rat.

The pharmacokinetics of 3-(decyldimethylsilyl)-N-[2-(4-methylphenyl)-1-phenylethyl]propanamide (DMPP), an inhibitor of acyl-CoA:cholesterol acyltransferase, have been studied in the dog and the rat using 14C and 3H dual-labelled drug. In both species, gastrointestinal absorption of DMPP was slow and incomplete, amounting to approximately 20 per cent of the oral dose given in corn oil. In the rat, use of PEG-400, Tween 80, ethanol, and aqueous CMC as vehicles resulted in similar or lower absorption than corn oil. Absorbed DMPP was rapidly and extensively distributed to body tissues. Data from the rat showed highest concentrations of radioactivity in the liver and spleen, while concentrations in the adrenals and lung also markedly exceeded circulating radioactivity levels. In both dog and rat. DMPP was completely metabolized prior to excretion. The routes of biotransformation involved hydrolysis of the amide bond, oxidation of the phenyl ring, and degradation of the decyldimethylsilyl propanoyl moiety. The metabolites of DMPP were excreted slowly, predominantly in the faeces. The elimination half-life of 14C was 105 h in the dog and 83 h in the rat, while that of 3H was approximately 32 h in both species.

Animals↗
PubMedDate not supplied

Disposition of fluvastatin, an inhibitor of HMG-COA reductase, in mouse, rat, dog, and monkey.

The physiological disposition of fluvastatin, a potent inhibitor of hydroxymethylglutaryl-CoA reductase and thus cholesterol synthesis, has been studied in the mouse, rat, dog, and monkey using 14C- or 3H-labeled drug. Oral doses of fluvastatin were absorbed at a moderate to rapid rate. The extent of absorption was dose-independent and was essentially complete in all four species studied. However, the drug was subject to extensive presystemic hepatic extraction followed by direct excretion via the bile, thus minimizing the systemic burden and yielding high liver/peripheral tissue concentration gradients for fluvastatin and its metabolites. Only at high doses far exceeding the intended human daily dose of ca 0.6 mg kg-1 did fluvastatin bioavailability approach unity, apparently due to saturation of the first-pass effect. Dose-normalized blood levels of fluvastatin and total radioactivity were higher in the dog than in the other species, suggesting a smaller distribution volume in the former. Fluvastatin was partially metabolized before excretion, the extent of metabolism being smallest in the dog and greatest in the mouse. The half-life of intact fluvastatin ranged from 1-2h in the monkey to 4-7h in the dog. Regardless of the dose or dose route, the administered radioactivity was recovered predominantly in feces, with the renal route accounting for less than 8 per cent of the dose. No tissue retention of radioactivity was observed, and material balance was essentially achieved within 96h after dosing.

Administration, Oral↗