European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Jan 1996
Randomized Controlled Trial Clinical TrialDose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine.
The purpose of this pharmacokinetic study was to investigate the dose-dependent inhibition of model substrates for CYP2D6, CYP2C19 and CYP1A2 by four marketed selective serotonin reuptake inhibitors (SSRIs): citalopram, fluoxetine, fluvoxamine and paroxetine. ⋯ This investigation confirms that paroxetine and fluoxetine are potent inhibitors of CYP2D6, that fluvoxamine and fluoxetine are moderate inhibitors of CYP2C19 and that fluvoxamine is a potent inhibitor of CYP1A2 in humans in vivo. The clinical prediction of interaction from single-dose experiments may have to take the degree of accumulation during steady-state after multiple doses into account.
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Eur. J. Clin. Pharmacol. · Jan 1996
Clinical Trial Controlled Clinical TrialImpact of quinidine on plasma and cerebrospinal fluid concentrations of codeine and morphine after codeine intake.
The analgesic effect of codeine depends on its O-demethylation to morphine via sparteine oxygenase (CYP2D6) in the liver and presumably also via this enzyme in the CNS. We studied the ability of quinidine, which is a potent inhibitor of CYP2D6, to penetrate the blood brain barrier and its possible impact on codeine O-demethylation in CNS. ⋯ Quinidine penetrates the blood brain barrier poorly, but quinidine pre-treatment leads to pronounced lowering of the cerebrospinal fluid concentration of morphine after codeine intake. However, the O-demethylation of codeine in CNS may not be totally blocked by quinidine.
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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.