European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Jan 1996
Replacement of (R)-methadone by a double dose of (R,S)-methadone in addicts: interindividual variability of the (R)/(S) ratios and evidence of adaptive changes in methadone pharmacokinetics.
Twenty-two patients receiving (R)-methadone maintenance treatment were switched to a double dose of (R,S)-methadone: blood samples were collected before and after the change, and the concentrations of the enantiomers were measured. In the second period, during racemic methadone treatment, important interindividual variability in the stereoselective disposition of the enantiomers of methadone was measured, with (R)/(S) ratios ranging from 0.63 to 2.40. This point should be taken into account particularly with respect to therapeutic drug monitoring of racemic methadone. ⋯ Although of small amplitude (16%), this decrease confirms previously described adaptive changes in methadone pharmacokinetics during racemic methadone maintenance treatment and may necessitate, in some patients, a dose adjustment.
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Eur. J. Clin. Pharmacol. · Jan 1996
Randomized Controlled Trial Clinical TrialHaemodynamic interactions of a new calcium sensitizing drug levosimendan and captopril.
Levosimendan in a new inodilator drug that sensitizes troponin C in heart muscle cells to calcium, thus improving contractility. In previous studies, a single 2 mg intravenous dose of levosimendan increased cardiac output (CO) in healthy volunteers by about 40% and decreased pulmonary capillary wedge pressure in heart failure patients by 40-50%. The aim of the present, double-blind study was to evaluate the safety of concomitant use of levosimendan and an ACE-inhibiting drug. ⋯ It seems that concomitant treatment with captopril does not change the haemodynamic effects of levosimendan. No adverse haemodynamic interactions were seen.
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Eur. J. Clin. Pharmacol. · Jan 1996
Clinical Trial Controlled Clinical TrialProgress in the prostaglandin E1-therapy of the intermittent claudication by means of bolus injections of LIPO-prostaglandin E1 (LIPO-PGE1).
We compared the efficacy of a bolus injection (5 min) of LIPO-PGE1 (Prostaglandin E1 in lipid emulsion) with conventional PGE1-cyclodextrin (PGE1-cyclodextrin) infusions (2 h) in patients with intermittent claudication. The quantitative blood-flow in the common femoral artery was measured using a computerized ultrasound Doppler system (MAVIS). We also monitored the transcutaneous oxygen pressure, the skin temperature on the foot, and the reactive change in blood pressure and pulse as well as side effects. ⋯ Dose finding of LIPO-PGE1: After bolus injection of 30, 50, and 80 micrograms LIPO-PGE1 a significant dose-dependent increase of the blood flow in the leg (+96.9%, 80 micrograms) with a peak 3 h after injection was seen. After LIPO-PGE1 we observed an enhanced microcirculation (significant rise in the transcutaneous oxygen pressure and the skin temperature on the foot). We noted longer lasting pharmacodynamic properties with LIPO-PGE1 (50 micrograms) compared to PGE1-cyclodextrin (60 micrograms). Comparison to PGE1-cyclodextrin: In a cross-over, placebo-controlled study, 20 patients with intermittent claudication received 4 weeks therapy with a bolus of 50 micrograms LIPO-PGE1 or a 2 h infusion of 60 micrograms PGE1-cyclodextrin per day. A significant increase in the blood flow was measured at the end of 4 weeks therapy compared to the initial values before treatment. This rise correlates significantly with the increase in the patient's maximal walking distance (+112%, LIPO-PGE1). Compared to conventional PGE1-cyclodextrin infusions given over 2 h, a clearly prolonged increase in perfusion of the affected limb after LIPO-PGE1 was demonstrated. No serious adverse effects were observed.
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Eur. J. Clin. Pharmacol. · Jan 1996
Randomized Controlled Trial Clinical TrialCodeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects.
Codeine O-demethylation to morphine is catalysed by the genetic polymorphic sparteine oxygenase (CYP2D6). The objective of the present study was to assess the analgesic effect of codeine on different types of experimental pain in relation to sparteine phenotype. ⋯ This study confirms that codeine O-demethylation depends on CYP2D6; it shows that the 6-glucuronidation of morphine is independent of CYP2D6; it supports the theory that the analgesic effect of codeine depends on its O-demethylation; and it indicates that this is probably also the case for the adverse effects. The results lend no support to the suggestion of a non-opioid analgesic effect of codeine.
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Eur. J. Clin. Pharmacol. · Jan 1996
Comparative StudyEffects of oral contraceptives on plasma neutral amino acids and cholesterol during a menstrual cycle.
Concentrations of plasma neutral amino acids, i.e. threonine, serine, asparagine, glycine, alanine, citrulline, alpha-aminobutyric acid, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, and tryptophan, and serum cholesterol, were determined at the follicular (Day 4), mid-cycle (Day 16) and luteal (Day 25) phases of the menstrual cycle in 15 users of the new generation of combined oral contraceptives (OC), 11 on multiphase combined OC, and 17 controls. ⋯ The results suggest that the metabolic effects of the new generation combined OC on neutral amino acids and cholesterol are only modest to slight, except for the effect on tyrosine, the brain noradrenaline precursor, which may cause disturbances of various noradrenaline-mediated central functions in susceptible subjects.