Search PubMed⌕ Search

Biomedical subjects

F Bochner

Publications and source records attributed to F Bochner.

139 records · Page 8Linked to original sources
PubMed1972

Effect of a delayed-action phenytoin preparation on blood phenytoin concentration.

In a cross-over study in a group of epileptic patients it was shown that replacement of the evening dose of an ordinary phenytoin preparation with the same phenytoin dose in a delayed-action preparation produced no significant change in the next morning's mean blood phenytoin concentration. However, replacement of the entire daily dose of an ordinary phenytoin preparation with the delayed-action preparation did increase mean blood phenytoin levels after some days, possibly because the latter preparation contained an additional 6% active drug, as compared with the former. In most circumstances, it seems doubtful if the delayed-action preparation offers any advantage over ordinary phenytoin in treating epilepsy.

Chromatography, Gas↗
PubMed1972

Effect of dosage increments on blood phenytoin concentrations.

Blood phenytoin (diphenylhydantoin) concentrations were measured after each dosage change in 12 epileptic patients who were given increasing oral doses of phenytoin. In each of these patients a dosage increment beyond the dosage that produced a blood phenytoin level of 6-9 μg/ml. caused a disproportionately great increase in the blood concentration of drug. This effect might be expected if the limit of the body's capacity to metabolize phenytoin were being reached. As oral dosages were increased in one patient, measurements of the rate of urinary excretion of phenytoin metabolite showed that the phase of rapid rise in blood phenytoin concentration coincided with a failure to increase the rate of phenytoin metabolite excretion. Awareness of the non-linear relation between oral dose and blood concentration of phenytoin in the individual patient, and realization that the phase of rapid rise in blood phenytoin concentration occurs through the `therapeutic' range of 10-20 μg/ml., is of importance to those who use blood phenytoin levels as a guide to the adequacy of anticonvulsant therapy.

Administration, Oral↗
PubMedDate not supplied

The relationship between the pharmacokinetics of ibuprofen enantiomers and the dose of racemic ibuprofen in humans.

Ibuprofen is a chiral drug which is used clinically as a racemate. The pharmacological properties of ibuprofen reside almost exclusively with the S(+)-enantiomer. However, a portion of R(-)-ibuprofen is metabolically inverted to its pharmacologically active, mirror-image form. To investigate the influence of increasing dose of racemic ibuprofen on the pharmacokinetics of its individual enantiomers, four healthy male volunteers were given racemic ibuprofen (200, 400, 800, and 1200 mg), orally, on four occasions. The study was conducted using a balanced cross-over design. The extent of absorption of ibuprofen, as assessed by the total urinary recovery of ibuprofen and its metabolites, was extensive and independent of the administered dose. At all four doses, the area under the total and unbound plasma concentration-time curves (AUC and AUCu, respectively), and the unbound fraction in plasma, were significantly greater for the S(+)-enantiomer. With increasing ibuprofen dose, there was a less than proportional increase in the AUC of each enantiomer, while the AUCu for both enantiomers increased in direct proportion to the administered dose. The time-averaged unbound fraction of each enantiomer increased significantly with increasing dose, which caused the non-linearity between AUC and dose. It was predicted that the metabolic intrinsic clearance of each enantiomer, and the fraction of R(-)-ibuprofen which was metabolically inverted to S(+)-ibuprofen, was independent of the administered dose.

Adult↗
PubMedDate not supplied

The elimination of phenytoin in man.

1. Plasma phenytoin (diphenylhydantoin) levels after different drug doses were correlated with urinary 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) excretions in four subjects. 2. In three of four subjects the proportion of the phenytoin dose that was excreted as p-HPPH. In the fourth, p-HPPH output remained proportionate to dose of phenytoin until elimination of the drug fell below its input. 3. Plasma p-HPPH levels were measured in two subjects; the data suggested that the renal excretion of p-HPPH was not rate-limited. 4. In three of four subjects, there was the possibility that alternative pathways for eliminating phenytoin may have developed as drug doses increased and the capacity for forming p-HPPH became saturated. 5. Overall phenytoin elimination appeared to approach saturation at concentrations of the drug encountered therapeutically. When Michaelis-Menten kinetics were applied to data for phenytoin elimination in twenty-one adults and fifteen children, the mean apparent Km value for the adults corresponded to a plasma drug concentration of 5-8 mug/ml, and in the children to 5-3 mug/ml. The mean Vmax values in the two groups were, respectively 8-1 mg/kg per day and 12-5 mg/kg per day.

Adolescent↗
PubMedDate not supplied

Renal tubular secretion of amiloride and its inhibition by cimetidine in humans and in an animal model.

The histamine H2 antagonist cimetidine has been shown to reduce the renal tubular secretion of other organic cations through competition for the specific transport system with organic cations in the renal proximal tubule. The potential interaction between cimetidine and the potassium-sparing diuretic amiloride was investigated in humans and in the isolated perfused rat kidney. A chronic dosing study was conducted in eight healthy subjects who received, in random order, amiloride (5 mg daily), cimetidine (400 mg twice daily), both drugs together, and a control phase in which no drug was present. Cimetidine reduced the renal clearance of amiloride by a mean of 17%, from 358 +/- 134 to 299 +/- 118 ml/min (p less than 0.05), and the urinary excretion of amiloride from 65 +/- 11 to 53 +/- 13% of the dose (p less than 0.05). Amiloride reduced the excretion of cimetidine from 43 +/- 7 to 32 +/- 9% of the dose (p less than 0.05) and the area under the plasma concentration-time curve for cimetidine by a mean of 14% (p less than 0.05) but had no effect on the renal clearance of cimetidine. In the perfused rat kidney, cimetidine reduced the amiloride unbound renal clearance to glomerular filtration rate ratio from 5-7:1 to 1-2:1 (p less than 0.05). These studies demonstrate that cimetidine inhibits the renal tubular secretion of amiloride in humans and in rats to a similar extent. In addition, in humans the gastrointestinal absorption of both amiloride and cimetidine appear to be reduced by each other, by an as yet unknown mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Drug advertising.

Explore the source record for details and available documents.

Advertising↗