PubMed Health⌕ Search

Biomedical subjects

H H Frey

Publications and source records attributed to H H Frey.

At least 73 records · Page 4Linked to original sources
PubMed1981

Interactions between chloramphenicol and intravenous anesthetics.

Chloramphenicol has been reported to prolong the action of barbiturate hypnotics by an inhibition of liver mixed function oxidases. We have studied the importance of this interaction for shortacting intravenous anesthetics the effect of which is terminated by distribution rather than metabolic inactivation. Mice were pretreated orally with 50 mg/kg chloramphenicol as the sodium succinate 1 h before the iv. injection of the anesthetics, and the sleeping times were compared to those of untreated controls. The duration of action of methohexital was prolonged when doses of 15 and 20 mg/kg were injected, but not with the lowest dose of 10 mg/kg. After injection of thiopental (30, 40 and 50 mg/kg) only the medium dose was prolonged the effect of etomidate (3 and 5 mg/kg), but not that of propanidid (60 mg/kg) or ketamine (30 and 40 mg/kg). The results show that the experimental finding of an interaction between chloramphenicol and barbiturates cannot be generalized: It will not play a major role with usual clinical induction doses the effect of which is terminated by distribution, but may be of importance when higher doses are administered.

Anesthesia, Intravenous↗
PubMed1981

Pharmacokinetics of naproxen in the dog.

The pharmacokinetics of naproxen was studied in mongrel dogs. After IV injection of a 5 mg/kg dose, plasma concentrations decreased biexponentially, with an average elimination half-life of 74 hours. The drug was highly protein-bound (greater than 99%) and had a correspondingly low apparent volume of distribution (0.13 L/kg). After naproxen was given orally, absorption was rapid, and the bioavailability ranged between 68% and 100%. With an initial dose of 5 mg/kg given orally, therapeutic plasma concentrations could be maintained by giving 1 daily dose of 1.2 to 2.8 mg/kg.

Administration, Oral↗
PubMed1981

Pharmacokinetics of diazepam in the dog.

After i.v. administration of 2 mg/kg diazepam to dogs, concentrations of unmetabolized drug showed a triexponential decline with an average elimination half-life t0.5(beta) of 3.2 hr. Desmethyldiazepam appeared rapidly in plasma and exceeded diazepam concentrations by far. Elimination half-lives of this metabolite averaged 3.6 hr. Oxazepam reached maximal plasma concentrations in the range of 100 ng/ml after about 2 hr which then declined with a half-life of 5.7 hr. When the sum of the concentrations of diazepam and its active metabolites was plotted against time, the curve could be fitted by an open 2-compartment model, so that one of the apparent 3 compartments in the distribution of diazepam must be assumed to represent first pass demethylation to desmethyldiazepam. After oral administration of the same dose, desmethyldiazepam concentrations exceeded those of diazepam from the first blood sample taken. The share of unmetabolized diazepam in the total area under curve was only 1-3% after oral administration, but 7-21% after i.v. administration. Oral bioavailability was in the range of 74-100%. By continued oral administration of 1 or 2 mg/kg diazepam t.i.d. it was possible to maintain steady state plasma concentrations of 1000-2000 ng/ml desmethyldiazepam and maximal diazepam concentrations of 100-800 ng/ml. Oxazepam did not exceed a concentration of 100-200 ng/ml and small concentrations of 3-hydroxydiazepam could also be detected in these experiments. There was no indication of enzyme induction by this dose regimen. Both diazepam and desmethyldiazepam rapidly passed the blood/CSF barrier and reached steady state concentrations is CSF corresponding to the part not bound to serum proteins.

Administration, Oral↗
PubMed1980

Clinical pharmacokinetics of phenytoin in the dog: a reevaluation.

The pharmacokinetics of phenytoin, as well as drug plasma concentrations, during continued treatment were studied in the dog. After IV injection of 10 mg/kg, the average elimination half-life was 4.4 hours, which is in good agreement with previous studies. Bioavailability from tablet formulation was rather poor (av 36% compared with that obtained with IV) and showed great variation between dogs. Even with the dosage regimen of 20 mg of drug/kg given TID orally, therapeutic plasma concentrations could only be maintained for the first 2 or 3 days of treatment; these subsequently decreased to ineffective concentrations during the 1st week of treatment. This effect was accompanied by considerable reductions in half-life, indicating that phenytoin is a strong inducer of microsomal drug metabolism in the dog. Phenytoin must be considered as poorly suited for the treatment of canine epilepsy.

Administration, Oral↗
PubMed1980

Pharmacokinetics of carbamazepine in the dog.

1. The pharmacokinetics of carbamazepine was studied in dogs after oral administration of two pharmaceutical preparations. Adsorption was rapid, however, the drug was much better absorbed from a liquid preparation than from tablets. Plasma concentrations declined with an elimination half-life of 1.5 hr. Carbamazepine-10,11-epoxide, which is equipotent with carbamazepine as an anticonvulsant, was rapidly formed and reached plasma concentrations higher than those of the mother compound. The concentrations of the epoxide remained high as long as plasma concentrations of carbamazepine were above 2--4 nmole/ml, then they fell with an average half-life of 2.2 hr. 2. During continued treatment with daily doses of 0.34--0.38 mmole/kg carbamazepine, plasma concentrations showed a pronounced and progressive decline from Day 2 which is considered as the result of induction of microsomal liver enzymes. 3. Carbamazepine and the epoxide pass into CSF at a rate comparable to that of phenobarbital or barbital and primidone, respectively. 4. Binding to serum proteins was about 70% for carbamazepine and 40% for the epoxide in dog serum; slightly higher values were found for human serum.

Animals↗
PubMed1979

Anticonvulsant action in a series of benzimidazole anthelmintics.

In mice, the electroconvulsant threshold was elevated after oral administration of 7 benzimidazole anthelmintics at a dose of 100 mg/kg. This effect was most pronounced with cambendazole which also showed an outstanding duration of action. None of the drugs tested elevated the pentetrazole seizure threshold.

Animals↗
PubMed1979

Pharmacokinetics of primidone and its active metabolites in the dog.

In dogs, the metabolism of primidone and the pharmacokinetics of the drug itself as well as its metabolites phenobarbital and phenylethylmalonic acid diamide (PEMA) was followed after single oral doses of 30 mg/kg (0.14 mmole/kg). Primidone was rapidly absorbed, so that maximal serum concentrations were reached after 2 hr, the concentration fell then with a half-life averaging 5 hr in Beagles and 10 hr in Mongrels. PEMA appeared in plasma with a ka of 0.003--0.005 min-1, reached maximal concentrations after about 6.5 hr in Beagles and 12 hr in Mongrels. The elimination half-life averaged 7.5 hr in Beagles and 14 hr in Mongrels. After single oral doses, phenobarbital could only be detected in low concentrations in some Beagles. Phenobarbital had an elimination half-life of 32 +/- 4.8 hr in Beagles and of 70 +/- 16 hr in Mongrels. During continued treatment with daily doses of 30--50 mg/kg primidone, steady-state concentrations of about 15 micrograms/ml (65 nmole/ml) were reached after 6--8 days, the PEMA concentrations showed rather pronounced fluctuations around average values of 8--10 micrograms/ml (39--49 nmole/ml), whereas the concentrations of primidone mainly remained below 5 micrograms/ml (23 nmole/ml). In mice, the anticonvulsant potency of the 3 drugs was determined: Elevations of the electroconvulsant threshold by 40 V were produced by 0.01 mmole/kg of phenobarbital, 0.017 mmole/kg of primidone or 0.37 mmole/kg of PEMA. Taking the anticonvulsant potency of the 3 drugs into consideration, phenobarbital is responsible for more than 85% of the total anticonvulsant activity during continued medication of primidone. The penetration of primidone and its metabolites into the cerebro-spinal fluid was followed: phenobarbital reached steady state levels already after 1--1.5 hr, primidone and PEMA not before 2.5 hr. The concentrations in CSF roughly corresponded to the free drug in plasma. On account of the similarities in metabolism and pharmacokinetics of primidone in dog and man, the former species seems to be a suitable model in epilepsy research. Differences between both species are most pronounced in the Beagle.

Animals↗