PubMed Health⌕ Search

Biomedical subjects

G Bozler

Publications and source records attributed to G Bozler.

At least 19 recordsLinked to original sources
PubMed1995

Pharmacokinetics and metabolic pattern after intravenous infusion and oral administration to healthy subjects.

Meloxicam [4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H- 1,2-benzothiazine-3-carboxamide-1,1-dioxide] is a new nonsteroidal antiinflammatory drug belonging to the enolic acid group. In a crossover study, 30 mg 14C-labeled meloxicam was administered to four male healthy volunteers as a short-term infusion and as an oral solution. The objectives of the study were to determine the mode of elimination, the excretion balance, the in vivo binding characteristics to serum proteins, and to investigate the metabolic pattern in plasma, urine, and feces. A comparison of plasma concentration measurements of unchanged drug by a specific HPLC assay and total radioactivity by liquid scintillation counting revealed a very close conformity. Over 90% of the plasma radioactivity was represented by unchanged drug. Its terminal and dominant half-life of elimination from plasma, as determined from plasma and urinary data in this study, ranged from 12 to 17 hr in the volunteers. The serum protein binding of the radioactivity from in vivo samples was very high (99.1-99.7%). The excretion balance was complete after 6 days. Average urinary excretion of 14C-radioactivity accounted for 43% of the dose, with the remainder appearing with the feces. Meloxicam was extensively metabolized, with only traces of the drug appearing unchanged in urine and feces. The main metabolites were formed by hydroxylation and further oxidation of the methyl group of the thiazolyl moiety. In addition, two further metabolites were found, particularly in urine. Altogether, > 95% of the dose excreted could be accounted for by the metabolites identified or the parent compound itself.

Administration, Oral↗
PubMed1990

Absolute bioavailability of pirenzepine in intensive care patients.

The absolute bioavailability (f) of pirenzepine was determined in 27 intensive care patients receiving the drug for prophylaxis and therapy of upper gastrointestinal tract bleeding. A multiple oral and intravenous dosage regimen and the times of blood sampling were adapted to individual conditions and treatment. Mean f in the patients was 0.28, which was significantly higher than in 12 normal subjects (0.14). It showed no dependence on age (range 20-82 y), nor on the risk factors cardiac insufficiency, renal and hepatic dysfunction, gastrectomy (Billroth II) and bleeding gastrointestinal ulcers, nor on concomitant administration of metoclopramide or antacids. Due to the wide therapeutic index of pirenzepine, it is concluded that individualization of therapy is not necessary for patients in intensive care.

Administration, Oral↗
PubMed1989

Steady-state intravenous pharmacokinetics of pirenzepine in patients with hepatic insufficiency and combined renal- and hepatic insufficiency.

The steady-state intravenous pharmacokinetics of pirenzepine has been investigated in patients with chronic liver disease and others with combined chronic liver disease and renal insufficiency. The plasma clearance (CL) of Pirenzepine, steady-state plasma concentration Cmin(ss) and dominant half life t1/2 gamma were not significantly altered in the chronic liver disease group. In patients with renal and hepatic insufficiency, CL was reduced, t1/2 gamma was prolonged from 11.1 to 19.4 h and Cmin(ss) was elevated from 36 ng/ml to 66 ng/ml compared to healthy controls. Plasma concentrations remained in the therapeutic range and the dosage regimen was well tolerated. Adjustment of the dose of pirenzepine need be considered only in cases of severe impairment of both renal and hepatic elimination.

Adult↗
PubMed1989

Steady-state intravenous pharmacokinetics of pirenzepine in patients with differing degrees of renal dysfunction.

The steady-state intravenous pharmacokinetics of pirenzepine has been investigated in 57 subjects whose renal function ranged from normal to chronic failure requiring regular haemodialysis. Pirenzepine renal clearance, total clearance and terminal (dominant) half-life were found to be correlated with the creatinine clearance (CLCR), but this was not the case for the volume of distribution and the nonrenal clearance. The therapeutic regimen was well tolerated by all subjects. Haemodialysis did not significantly contribute to the elimination of pirenzepine. Dosage adjustment need only be considered in patients with CLCR less than 25 ml/min in order to reduce the frequency of minor side-effects.

Adolescent↗
PubMed1987

Pharmacokinetics of pirenzepine in patients with gastric or duodenal ulcers.

1. The pharmacokinetics of pirenzepine (Gastrozepin) was studied after single and multiple oral administration in gastric ulcer and duodenal ulcer patients. 2. With a dose of 50 mg of pirenzepine, plasma levels reached a maximum 2 h after the administration in both groups (gastric ulcer patients: 57.2 +/- 31.8 ng/ml, duodenal ulcer patients: 48.0 +/- 18.0 ng/ml), and decreased bi-phasically with an elimination half-life (t1/2 beta) of 13.9 +/- 4.0 and 17.9 +/- 4.5 h, respectively. The area under the plasma level curve were 844 +/- 319 ng X h/ml and 663 +/- 151 ng X h/ml in the respective group. 3. The plasma levels of pirenzepine after multiple administration (50 mg was given as a loading dose, and thereafter 25 mg was given as a maintenance dose at an interval of 12 h for 7 days) maintained certain steady state levels from just after the start of administration. 4. It can be concluded that there is no significant difference in the pharmacokinetics of pirenzepine between gastric and duodenal ulcer patients. It can be judged that twice-daily administration of pirenzepine is enough for ulcer treatment.

Administration, Oral↗
PubMed1982

Pharmacokinetics of oral dipyridamole (Persantine) and its effect on platelet adenosine uptake in man.

Two preparations of dipyridamole have been studied by oral administration to 11 normal volunteers. The plasma levels of dipyridamole and its glucuronide were determined simultaneously by high performance liquid chromatography. The instant form (I.F., 100 mg) was administered four times daily and the slow release preparation (SRP, 200 mg) twice daily, for 3 days. Multiple blood samples were collected on Days 1-4 to provide plasma for assay, and simultaneously, platelet rich plasma was prepared for ex vivo study of the effect of dipyridamole on platelet uptake of adenosine. The pharmacokinetics of absorption and distribution of dipyridamole were described using a two compartment model with lag time and prolonged absorption. Strong inhibition of the platelet adenosine uptake was observed at therapeutic plasma levels. The inhibition of platelet adenosine uptake may be related to some of the pharmacological properties of dipyridamole.

Absorption↗
PubMed1982

Compartment model of prenalterol.

In previous pharmacokinetic studies in healthy subjects the time course of plasma concentration of prenalterol was described by a short distribution phase (alpha-phase) with a mean half-life of about 8 minutes and an elimination phase (beta-phase) with an average half- life of about two hours [1, 2]. The aim of this joint study was to check the pharmacokinetic data obtained after intravenous single dose administration with the computer program TOPFIT [3] using different compartment models and to test the predictive power of the chosen kinetic model for plasma concentration data after repetitive intravenous prenalterol dosing.

Adrenergic beta-Agonists↗
PubMed1981

Pharmacokinetics of oxazepam following multiple administration in volunteers and patients with chronic renal disease.

The plasma level course and the elimination of oxazepam (Adumbran) via urine were investigated following multiple oral administration in volunteers and patients with chronic renal failure. Additionally, drug metabolizing enzyme systems had been induced in the volunteers by pretreatment with phenobarbital. The plasma protein binding in vitro of oxazepam was determined in volunteers and patients. The plasma levels and the renal elimination of oxazepam and its metabolites do not show any differences between the two groups of volunteers (oxazepam and oxazepam after pretreatment). 83--92% of the dosage are eliminated via urine. In comparison, the plasma levels of oxazepam in patients with renal failure are half those of the volunteers. However, the plasma levels of oxazepam metabolites in patients are much higher than in volunteers and these increases correlate to the creatinine clearance of the patients. The non-protein bound oxazepam in plasma was found to be twice as high in the plasma of patients as that of volunteers. As a consequence, the lower plasma level of oxazepam in patients will be compensated for so that the pharmacological activity in patients and volunteers due to free oxazepam in the plasma water is nearly the same. Therefore a new dosage regimen for treatment with oxazepam in patients with renal failure is not necessary.

Adult↗
PubMed1980

An international pharmacokinetic study on pirenzepine following a single oral dose.

Pirenzepine is a very hydrophilic compound. As a consequences its penetration through biomembranes and hence its absorption after oral administration is limited. The variability in plasma pirenzepine after a single oral dose of 50 mg (2 x 25 mg tablet) was investigated in ten countries in a total of 87 volunteers. Pirenzepine was measured by a specific radioimmunoassay. Plasma level profiles were similar in every country with a peak of about 50 ng/ml within two hours after the dose. The mean terminal half-life of disposition was 11 hours. Although the area under the plasma level curve was not normally distributed throughout the population, there was a narrow distribution around the median. It is often accepted that drugs or drug formulations with low bioavailability show high variations in the rates and extent of absorption. Pirenzepine, however, shows consistently uniform plasma level profiles, well within the therapeutic range after multiple dosing (50 mg, twice daily). Only a small proportion of the population may need individual adjustment of the conventional dose regimen.

Administration, Oral↗
PubMed1978

[Ambroxol, comparative studies of pharmacokinetics and biotransformation in rat, rabbit, dog and man (author's transl)].

Pharmacokinetics and biotransformation of trans-4-(2-amino-3,5-dibromo-benzylamino)cyclohexanol hydrochloride (ambroxol, NA 872 Cl) was studied using the 14C-labelled compound. Absorption after oral administration was found to be fast and complete. Elimination half-life of radioactivity in the blood was estimated as 20--25 h in rat, dog and man and as 2 h only in rabbit. This apparent elimination half-life is governed by the disposition of acidic metabolites of NA 872. In man and rabbit radioactivity is excreted almost completely into the urine, whereas in rat and dog biliary excretion is also observed. Routes of biotransformation are similar in all 4 species. NA 872 is metabolized by phase I reactions to NA 873 and finally to dibromoanthranilic acid. Phase II reactions with the parent compound and metabolites are observed mainly in man and rabbit.

Ambroxol↗
PubMed1978

[Ambroxol, studies of biotransformation in man and determination in biological samples (author's transl)].

15 mg trans-4-[2-amino-3,5-dibromo-benzyl)-amino]-cyclohexanol-hydrochloride (ambroxol, NA 872) was administered i.v. and orally to healthy volunteers. The metabolic pattern in urine and plasma was similar for both routes of administration. Biotransformation reactions are straightforward, yielding two major products of phage I reactions identified as 6,8-dibromo-3-(trans-4-hydroxycyclohexyl)-1,2,3,4-tetrahydro-quinazoline and 3,5-dibromo-anthranilic acid. These metabolites as well as the parent compound are also converted to conjugates, predominantly glucuronides. Quantification of unlabelled ambroxol in biological fluids is achieved by radiochemical derivatisation with 14C-labelled formaldehyde in imitation of the biotransformation.

Administration, Oral↗
PubMed1977

[Studies on the pharmacokinetic equivalence of pivampicillin base and hydrochloride in capsules and tablets (author's transl)].

Absorption and urinary excretion of pivampicillin as hydrochloride and as base were studied following administration of four different formulations to 12 healthy volunteers in a cross-over study. A fluorimetric assay of ampicillin was adapted to be used with an Auto Analyzer system. The plasma concentrations observed are comparable to those reported in the literature. The amount of drug absorbed is the same for all four medications whereas absorption is more rapid from tablets than from capsules. Base and hydrochloride of pivampicillin are equivalent with respect to pharmacokinetic behaviour. So, the formulation itself seems to be more important for biological equivalence than the ionisation of the drug used in the formulation.

Ampicillin↗
PubMed1977

[Model building in pharmacokinetics/Part II: Generalized theoretical presentation of complete integration of linear compartment models of optional structure (author's transl)].

The method of Laplace transformation is used to obtain the integral of linear differential equations for pharmacokinetic models. A general solution uniform in structure for all types of models (mammillary, catenary, mixed) was established. Choice of one more application compartments, of kinetics describing the input procedure and of elimination pathways is free.

Kinetics↗