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I Janků

Publications and source records attributed to I Janků.

At least 37 records · Page 2Linked to original sources
PubMed1986

Pharmacokinetics of temocillin after intravenous and intramuscular administration.

Pharmacokinetics of temocillin (BRL 17421) was studied in a crossover study in 10 male healthy volunteers after administration 1 g of temocillin intravenously or intramuscularly. The mean serum levels of temocillin at the 5th min after i.v. administration were 131.57 mg/ml, at 1 h 71.27 mg/l and at 12.12 mg/l. The values of the pharmacokinetic parameters were as follows: AUC 509.2 mg X h X l-1, t1/2 4.2 h-1, Vd ss 11.57 l, Vd area 12.28 l, CL 2049 ml X h-1. The urinary excretion by 12 h was 70.58% of the administered dose of temocillin. The mean serum levels of temocillin after i. m. administration were at 2 h 46.65 mg/l and at 12 h 15.89 mg/l, the corresponding pharmacokinetic parameters were: AUC 501.38 mg X h X l-1, t1/2 4.3 h-1, Vd 12.69 l. The urinary excretion by 12 h was 57% of the administered dose of temocillin. It follows from the study that pharmacokinetic parameters of temocillin after both ways of temocillin administration are very closed and that the dose 1 g of temocillin is sufficient to create effective serum levels for the majority of sensitive gramnegative organismus.

Adult↗
PubMed1986

Possible effects of muramyl dipeptide on liver cell membranes.

Three different approaches were utilized for illustration of membranous effect of muramyl dipeptide (MDP) on liver cells. Toxicologic approach using a hepatoprotective effect against CCL4 as well as from previous results with other toxins. Histochemistry and microfluorometry after chemical injury. Biochemical as assessed by modulation of 14C palmitic acid incorporation under MDP effects in neutral lipids and phospholipids content of cell membranes. By this integrated study we may assume MDP played a role in one or more cell membrane(s). This assumption was supported by reduction of hepatocyte injury as assessed by enzyme analysis in serum or in the cells. Moreover, MDP pretreatment influenced the increase in the incorporation of labeled palmitic acid in neutral lipids and phospholipids. Microscopical image analysis and histochemical results supported the aforementioned findings.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Kinetics of transport and metabolism of 1-beta-D-arabinofuranosylcytosine and structural analogs by everted perfused rat jejunum.

Few reports have dealt with the kinetics and metabolism of AraC and analogs by rat intestine. Using everted rat jejunum with continuous perfusion, it was possible to demonstrate that AraC and Cyd cross the intestinal barrier(s) by a carrier mediated process which was saturable and exhibited fairly good fitting of the flux rate by Michaelis-Menten equation. The transport rate of different analogs was not consistent with the pH-partition theory of membrane transport of drugs being rather dependent on the chemical structure of the nucleoside. A free amino group of cytosine increased the rate of transport within the present series of AraC analogs. There was a detectable deaminase as well as esterase activity towards AraC and its analogs in rat jejunum.

Animals↗
PubMed1984

Structure-intestinal transport and structure-metabolism correlations of some potential cancerostatic pyrimidine nucleosides in isolated rat jejunum.

Both transport and biotransformation processes for a series of pyrimidine nucleobases, ribonucleosides, 2'-deoxyribonucleosides, and acetyl and 5'-substituted derivatives of the cancerostatic agent araC were studied in the isolated everted rat jejunum with a continuous perfusion technique. Metabolic alterations during penetration were assessed by HPLC. 5'-Halogeno and 5'-deoxy derivatives of cytosine nucleosides exhibited higher transport rates and higher stability towards the deamination reaction than did unsubstituted derivatives. Octanol-buffer partition coefficients were estimated for the study compounds, and fragmental constants for the sugar moieties of nucleosides were assessed. With the present study compounds there was no correlation between lipophilicity and transport rate, as previously reported, but there was a correlation between lipophilicity and metabolic alteration of araC derivatives (r = 0.99, n = 5).

Animals↗
PubMed1983

Changes in electroretinogram and serum potassium during L-DOPA treatment in parkinsonism.

The relationship of L-DOPA plasma level, parameters of ERG and severity of extrapyramidal symptoms after a single dose of L-DOPA was investigated in 11 patients suffering from parkinsonism of idiopathic or arteriosclerotic origin. After a drug-free night, each patient received his/her usual morning dose of L-DOPA. In the subsequent 3 h, the ERG recordings, blood levels and clinical ratings of extrapyramidal symptoms significantly dropped after a delay of 60 min in relation to the occurrence of the peak plasma L DOPA level. The initial "b" wave amplitudes as well as initial serum potassium values were abnormally high. There was a statistically significant correlation between the decrease of "b" wave amplitude (delta "b") and the potassium "normalization index" (i.e. the ratio between the observed decrease of serum potassium and the pretreatment difference from the middle normal potassium value). A definite interpretation of the data cannot be provided until more knowledge about the origin of "b" wave of ERG is available. It can be concluded tentatively that dopaminergic processes influence electrophysiological reactivity of the retina.

Aged↗
PubMed1983

Biotransformation of drugs in rats treated with a synthetic muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP).

Natural immunoadjuvant mixtures like BCG and FCA are known to produce gross alterations of drug-metabolizing systems in the rat. Since it has been shown that the smallest structure of various bacterial peptidoglycans, possessing adjuvant activity, is muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), the possibility has been tested whether this substance is involved in production of the observed metabolic changes. Synthetic compound was applied subcutaneously for the period of 21 days, and the in vitro activity of 7-ethoxycoumarin-O-de-ethylase, aminopyrine-N-demethylase, together with the microsomal content of cytochrome P-450 and b5, and the in vivo acetylation of sulphadimidine, were investigated. No effect of MDP on any of these tests was noted in both the Lewis arthritic strain and the AVN disease-free strain. It is suggested that MDP is metabolically inactive and that the defects in metabolism of drugs, following bacterial-adjuvant treatment, are likely to be due to some additional cell-wall components, other than peptidoglycans. Furthermore, our data support the view of no relationship between the development of metabolic changes and the established arthritic lesions in rats.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Pharmacokinetics of antituberculosis drugs after oral isolated and simultaneous administration in triple combination.

On the basis of a mathematical analysis of the time course of the drug distributed in the organism there were studied pharmacokinetics of antituberculosis drugs after an isolated oral administration of doses used in daily treatment of tuberculosis, in INH, RMP, EMB, PZA, ETA, CS and TZ, and after a simultaneous--single and repeated--administration of INH, RMP, EMB in a triple combination, after the usual daily doses and after increased intermittent doses administered twice weekly. At first there were determined, with the use of chemical methods, blood concentrations of the antituberculosis drugs studied and their excretion with urine in an unchanged form. The results were analyzed pharmacokinetically by means of a one- compartment model with absorption. By an iteration process, based on non-linear regression analysis, the following pharmacokinetic parameters were calculated: Vd, Ka, Ke, T0.5 abs, T0.5 el, Tmax, Cmax, Clp tot and AUC. Their comparison revealed the following facts: The microbiologically most effective antituberculosis drugs--INH and RMP--are comparable even from the point of view of pharmacokinetics on account of similar pharmacokinetic parameters; in comparison with them EMB has half the size of the AUC, characterizing the efficacy of the drug. In this parameter PTA exceeds more than twice ETA; CS and TZ have a low Ke as well as Clp tot and a high T0.5 el, which is indicative of an insufficient excretion of both drugs. Pharmacokinetic parameters of PZA confirm the possibility of using the dose of 25 mg/kg in the treatment of tuberculosis. A simultaneous administration of the triple drug combination under study influences pharmacokinetic parameters of all the three antituberculosis drugs--it significantly decreases Ka as well as Ke, increases T0.5 el, Tmax, Vd and in INH also Clp tot, but only after a repeated administration. An intermittent administration of the mentioned triple drug combination significantly increases the area under the curve AUC in all the three antituberculosis drugs. This explains the same efficacy of higher doses of antituberculosis drugs, administered twice weekly, in comparison with a daily administration of lower doses of the same combination. The pharmacokinetic process of orally administered antituberculosis drugs can be analyzed according to a one-compartment model of pharmacokinetics, although the kinetics of certain antituberculosis drugs probably proceed in the organism in a more complicated way.

Administration, Oral↗