Determination of pethidine in rabbit plasma by capillary gas chromatography.

A simple and fast gas chromatographic method for the determination of pethidine hydrochloride in rabbit plasma is described and validated. This method is an improvement on the GC method which uses a glass column, and was described previously by Koska et al. [Anaesth. Analg. 60 (1981) 8]. The samples were analysed by a GC 5890 HP system using Rtx-5, fused-silica capillary column linked to a nitrogen-phosphorus ionization detector. Lidocaine hydrochloride was used as the internal standard. Calibration curves were linear within the range 5-200 ng/ml. The limit of quantification was about 5 ng using a 1-ml biological sample and no interference was observed in the blank plasma. The mean recovery of the drug from plasma samples was 95.71+/-2.82%. This procedure turned out to be sensitive and convenient enough for the use in pharmacokinetic studies of pethidine.

The influence of lidocaine on the permeability of the blood-cerebrospinal fluid barrier in experimental acute hypercapnia in the rabbit.

In a previous study we have provided evidence, that acute experimental hypercapnia due to hypoventilation in the rabbit alters blood-cerebrospinal fluid barrier function in the brain (Pakulski et al. 1998). The purpose of this study therefore was to determine if lidocaine would prevent the observed alterations in the blood-cerebrospinal fluid barrier function. The experiments were conducted in 16 adult Chinchilla rabbits submitted to acute hypercapnia due to mechanical hypoventilation (PaCO2 between 8-9.5 kPa over 180 minutes) under pentobarbital anaesthesia. The studied group (n = 8) was treated by lidocaine infusion 10 mg kg-1 h-1. After 180 minutes of hypercapnia the value of cerebrospinal fluid-blood index of gentamycin concentration, indicating the permeability of the blood-cerebrospinal fluid barrier, was significantly lower in animals treated with lidocaine (4.03 +/- 2.32 vs. 19.05 +/- 5.49; P < 0.01). We conclude that lidocaine may attenuate the increase of blood-cerebrospinal fluid barrier permeability under conditions of experimental acute hypercapnia lasting 180 minutes in the mechanically ventilated rabbit.

Pharmaceutical availability of clobetasol-17-propionate from cream and ointment.

Kinetics of drug release from both compared preparations available as a cream and an ointment, was in vitro studied. A reversed-phase HPLC method was developed for the determination of clobetasol-17-propionate in lipophylic bases using clobetasol-17-butyrate as an internal standard. Analyses were performed using a C18 reversed-phase column with a mobile phase of methanol-water and ultraviolet detection at lambda=254 nm. The calibration curve was constructed for the concentration range 0.5-40.0 microg/ml. The method is simple, accurate and precise.

Bioavailability of tramadol hydrochloride from tramadol--capsules 50 mg.

UNLABELLED: The aim of this study was to investigate the bioavailability of tramadol hydrochloride after oral administration of Tramadol--50 mg capsules, made in Synteza Pharmaceutical-Chemical Company in Poznan. As a reference preparation of Tramadol was used Tramal--50 mg capsules, (Grünenthal, Germany). The preparations were investigated in 20 healthy volunteers, according to a randomised two-way, cross-over design in the fasted state. Blood samples for determination of tramadol plasma concentrations were collected at pre-defined time points up to 24 h following drug administration. A washout period of one week separated both treatment periods. Tramadol plasma concentrations were determined by means of a validated HPLC method (fluorescence detector, verapamil as an internal standard). Values of 1,226.4 ng h/ml (Tramadol) and 1,397.01 ng x h/ml (Tramal) for the parameter AUC(0-infinity) demonstrate a nearly identical extent of drug absorption. Maximum concentrations--Cmax (217.81 ng/ml and 246.0 ng/ml) and time to reach maximum plasma concentration--Tmax (2.14 and 2.31 h) achieved for Tramadol and reference preparation did not differ significantly. CONCLUSIONS: the bioavailability of tramadol hydrochloride after administration of Tramadol is the same as after administration of Tramal, whose clinical efficacy was tested before.

[Carbamazepine presence in plasma lipoproteins]. / Dyspozycja karbamazepiny w lipoproteinach osocza.

The aim of this study was to define the disposition of carbamazepine (CBZ) in serum lipoproteins. The examination was conducted using the serum of 51 patients treated with carbamazepine the concentration of which was monitored 51 patients, 22 women and 29 men, 1.5-35 years old/mean 13.0 +/- 6.7 years/weighing 10.2-90.0 kg/mean 46.5 +/- 23.6/participated in the study. Every patient received carbamazepine in an individual oral dose. Concentrations of cholesterol, triglicerides, proteins and CBZ were determined. Lipoprotein fractions (VLDL, LDL, HDL and LPDS) were separated by ultracentrifugation of serum. Carbamazepine concentrations were measured by fluorescence polarization immunoassay technique on a TD x analyzer. Cholesterol, triglicerides and proteins levels were measured on Bayer--Technicon apparaturs. Carbamazepine is distributed in plasma lipoproteins, mainly in HDL fraction (mean 45.2 +/- 9.0%) and in LPDS (mean 43.2 +/- 9.3%) fraction. Ratio of carbamazepine concentration to cholesterol (RcCH), triglicerides (RcTG) and proteins concentration (RcP) and carbamazepine concentration (%) to cholesterol (R% CH), triglicerides (R% TG) and proteins concentration (%/R% P) are different in different fractions. The obtained results suggest that the disposition of CBZ in lipoprotein fractions may have a significant importance in the therapy and fat metabolism disorders make the changes of drug dose urgent.

[Pharmacokinetic aspects of geriatric therapy]. / Farmakokinetyczne problemy terapii geriatrycznej.

Some pharmacokinetic aspects of geriatric therapy were showed. Influence of alterations of physiological processes (changes of protein and lipid metabolism, failure of blood circulation and of renal function) in old age, on pharmacokinetics of drugs applied in geriatric pharmacotherapy (antibiotics, antiarrhythmic drugs, hypotensive drugs) were discussed. In this context, principles of rational pharmacotherapy of geriatric patients were proposed.

[Vitamin D3]. / Witamina D3.

Pharmacokinetic and pharmacodynamic properties of vitamin D3 were described. Clinical aspects of application were also revealed.

[The evaluation of the bioavailability of isosorbide 5-mononitrate]. / Ocena dostepnosci biologicznej 5-monoazotanu izosorbidu.

UNLABELLED: The aim of this study was to investigate the bioavailability of isosorbide mononitrate (IS-5MN) after oral administration of Monocard 20 mg-capsules, made in "Synteza" â Pharmaceutical-Chemical Company in Poznan. Effox 20 mg, coated tablets from Schwarz Pharma, was used as an counterpart of Monocard 20 mg. The concentrations of IS-5MN in healthy volunteers' plasma were determined by using Hewlett Packard gas chromatography. CONCLUSIONS: The bioavailability of IS-5MN after oral administration of Monocard 20 mg is the same as after oral administration of Effox 20 mg, whose clinical efficacy was tested before. This conclusion confirms the same value of AUC, tmax, cmax and other pharmacokinetic parameters of Monocard 20 mg and Effox 20 mg.

[Gentamicin level in the prostate and its pharmacokinetics in patients with benign prostatic hypertrophy]. / Stezenie w gruczole krokowym i farmakokinetyka gentamycyny u chorych z lagodnym przerostem gruczolu krokowego.

The study involved 15 male patients with periurethral prostatic adenoma without complete anuresis. The patients were given 80 mg of gentamicin intramuscularly one day before surgery and 80 mg in a one-hour infusion immediately before an operation. Gentamicin blood concentrations were measured. Pharmacokinetic parameters were calculated and dosage schemes for each patient basing on the antibiotic blood levels. Gentamicin levels in removed adenomas were also determined. Adenomas weighed between 18.0 and 45.8 grams while gentamicin concentration ranged from 1.31 to 3.8 micrograms/mL. It was found that gentamicin concentration in adenomas depend upon their weight. Moreover, pharmacokinetic parameters of this antibiotic exert negligible effect on its levels in adenoma.

[Evaluation of biological availability and anti-arrhythmic effect of a new drug Phenytoinum "Polfa"]. / Ocena dostepnosci biologicznej i dzialania przeciwarytmicznego nowego preparatu Phenytoinum "Polfa".

Studies were performed in 15 patients with ventricular arrhythmia. During the first day, the patients received 1000 mg of a new micronised form of Phenytoinum "Polfa" or adequate dose of a foreign drug in 3 doses every 3 hours and subsequently during 10 days alternatively native or foreign drug in a daily dose 300 mg. Twenty-four EKG Holter monitoring and determination of serum drug level were carried out after a 10-day treatment; area under the curve (AUC) in one 8 h dose interval was determined. Studies have shown usefulness of a new form of Phenytoinum (Polfa). Blood serum drug levels near to the therapeutic ones were observed. Steady-state Phenytoinum concentration was 11.1 +/- 5.9 micrograms/ml and after foreign drug it was 11.7 +/- 6.1 micrograms/ml, AUC0-8 was 90.4 and 105.3 micrograms/ml/h respectively. In 9/15 patients (60%) Phenytoinum (Polfa) produced substantial improvement in the cardiac arrhythmia.