Pharmacokinetics of clodronate in renal failure.

The pharmacokinetic parameters describing the fate of one intravenous clodronate (disodium dichloromethane diphosphonate) dose was studied in 24 normal subjects and in 24 patients with different degrees of renal insufficiency. The aim of the study was to derive data for adjustment of dosage in relation to renal function. Disodium clodronate in serum and urine samples was analyzed by capillary gas chromatography with mass-selective detection.

Rapid normalization of antipyrine oxidation by heme in variegate porphyria.

Effects of heme on hepatic xenobiotic drug metabolism were investigated in eight subjects with variegate porphyria. A single infusion of heme arginate (3 mg/kg heme) reversed rapidly the prolonged mean elimination half-life of antipyrine from 27.2 to 12.

A controlled study with taltrimide and sodium valproate: valproate effective in partial epilepsy.

Taltrimide was compared with valproate and placebo in 17 patients with intractable epilepsy being on carbamazepine monotherapy. Taltrimide (400 mg/day), valproate (1000 mg/day) or placebo were added to the treatment for periods of 3 months using a randomized cross-over design. Serum carbamazepine concentrations remained within the therapeutic range throughout the trial.

Haem arginate improves hepatic oxidative metabolism in variegate porphyria.

1. The elimination of antipyrine was investigated before and after intravenous administration of haem arginate (3 mg haem kg-1 day-1 on three or four successive days) to six patients with variegate porphyria in remission. 2.

Bioavailability of rectally administered carbamazepine mixture.

The relative bioavailability of carbamazepine mixture was studied after oral and rectal administration to healthy subjects. The absorption was significantly slower after the rectal than after the oral route but the total bioavailability was similar provided the mixture was not defaecated within 2 h of administration. We conclude that carbamazepine can be administered rectally, e.

Haem arginate: a new stable haem compound.

Intravenous administration of haem in acute hepatic porphyrias inhibits the induction of delta-aminolaevulinic acid synthase, reduces the formation of potentially harmful metabolites of porphyrin synthesis and corrects the haem deficiency. Typically, haem therapy has been given in the form of haematin--haem dissolved in alkali. Such haematin solutions are, however, extremely unstable.

Biochemical and clinical studies on epileptic patients during two phase I trials with the novel anticonvulsant taltrimide.

Taltrimide (2-phthalimidoethanesulphon-N-isopropylamide), a lipophilic derivative of taurine and a potent anticonvulsant in animal studies, was administered in daily doses of 1 and 2 g for 2 weeks with an interval of 2.5 months in 2 phase I clinical trials to 9 drug-resistant epileptic patients. Seizures and EEG were recorded, and routine laboratory studies conducted.

The effects of haem arginate and haematin upon the allylisopropylacetamide induced experimental porphyria in rats.

Biochemical disorders caused by allylisopropylacetamide in various animal species resemble human acute intermittent porphyria. The antiporphyrogenic efficacy and potency of haem arginate, a new haem compound, were compared with those of haematin in experimental porphyria of rats. Both haem arginate and haematin dose-dependently decreased the urinary excretions of porphyrin precursors.

Effects of repeated intravenous administration of haem arginate upon hepatic metabolism of foreign compounds in rats and dogs.

Haem arginate is a new haem compound, recently introduced for the treatment of acute hepatic porphyrias. Porphyrias are characterized biochemically by decreased formation of haem due to defects in certain enzyme activities involved in the haem biosynthesis. Haem is essential for cell respiration and oxidative biotransformation.

Effects of taltrimide, an experimental taurine derivative, on photoconvulsive response in epileptic patients.

Taltrimide is a lipophilic taurine derivative with definitive anticonvulsive effects in experimental epilepsy models. In this study, taltrimide was administered for 6 days, and the effects of the treatment on photoconvulsive response in EEG in eight epileptic patients were evaluated. Discharges provoked by intermittent photic stimulation (IPS) were increased by greater than 50% in four patients after taltrimide treatment.

Fate of haem after parenteral administration of haem arginate to rabbits.

Rabbits were injected either intravenously or intramuscularly with [14C]haem arginate and [59Fe]haem arginate (haem 5 mg kg-1). The main part (80%) of AUCINF of labelled haem was associated with the beta-phase, T1/2 being about 6 h. Only 1% of the haem dose had been taken up by the red blood cells.

Barbiturate and ethanol sleeping times and pharmacokinetics of propranolol in mice after intravenous administration of haem arginate.

Haem arginate is a new haem compound recently introduced for treatment of porphyrias. Previously haematin has been reported to increase certain hydroxylase activities in extrahepatic tissues, but even in therapeutic doses it impairs the microsomal foreign substance metabolism in the liver. Haem arginate at a dose equivalent to haem 10 mg/kg (threefold therapeutic dose) did not prolong the hexobarbital sleeping time of mice, 20 mg/kg did prolong the hexobarbital and possibly also the ethanol sleeping time.

Pharmacokinetics of intravenously administered haem arginate.

The pharmacokinetics of haem were investigated after intravenous administration of a therapeutic dose of haem arginate (3 mg haem kg-1) to four healthy volunteers and four symptomless porphyric patients. Plasma haem concentrations were measured also during a treatment course of four infusions in six patients with porphyria. Plasma haem concentrations declined monoexponentially over 48 h in both healthy volunteers and porphyric patients, with a mean +/- s.

Clinical trial with an experimental taurine derivative, taltrimide, in epileptic patients.

The antiepileptic effect, effects on EEG, and tolerability of taltrimide, a new taurine derivative, were studied in this open clinical trial in 27 patients with severe epilepsy resistant to conventional drugs. After the 2-week control phase, taltrimide was given in gradually increasing doses up to 4.0 g/day--this dose used for 12 days.

Methionine in paracetamol tablets, a tool to reduce paracetamol toxicity.

The analgesic effect, toxicity and kinetics of oral paracetamol were compared with those of paracetamol + l-methionine (5:1). The analgesic effect of paracetamol, studied in the Randall-Selitto test in rats, was not changed by methionine: ED50 was 94.6 mg/kg without methionine and 94.

Tolfenamic acid, metoclopramide, caffeine and their combinations in the treatment of migraine attacks.

Tolfenamic acid is a fenamate which inhibits prostaglandin (PG) biosynthesis and may act as a PG antagonist as well. Caffeine and metoclopramide are used in combination with analgesics and ergotamine in the treatment of migraine attacks, but controlled clinical studies on fixed combinations with analgesics are rare. The effects of orally given tolfenamic acid (200 mg), caffeine (100 mg), metoclopramide (10 mg), tolfenamic acid + caffeine (200 mg + 100 mg), tolfenamic acid + metoclopramide (200 mg + 10 mg) and placebo were studied in 49 migraine patients (3 men, 46 women) in a double-blind randomized cross-over study comprising 482 migraine attacks.

Drug treatment of motion sickness: scopolamine alone and combined with ephedrine in real and simulated situations.

In two placebo-controlled, double-blind, randomized trials scopolamine (0.3 mg) alone or combined with ephedrine (25 mg) was tested for its effectiveness in the prevention of seasickness during 24 h at sea and of motion sickness in rotating chair tests in a laboratory. Scopolamine was effective both alone and in combination with ephedrine, which supports the hypothesis on central cholinergic overactivity in the pathogenesis of motion sickness.

Pharmacokinetics of tolfenamic acid: disposition in bile, blood and urine after intravenous administration to man.

To study its pharmacokinetics and especially microCi/100 mg was infused i.v. in 8 patients with a T-tube inserted in the common bile duct at choledocholithotomy 7-10 days prior to the study.

Calcium, vitamin D and anabolic steroid in treatment of aged bones: double-blind placebo-controlled long-term clinical trial.

In a double-blind trial, 327 patients (57 men) over 65 (mean age 79.5) years received all possible combinations of calcium carbonate 3 g, vitamin D3 1000 iu, methandienone 2.5 mg and/or placebos daily for 9 months.