British journal of clinical pharmacology
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Br J Clin Pharmacol · May 2008
Transfer of chloroquine and desethylchloroquine across the placenta and into milk in Melanesian mothers.
The literature on placental and milk transfer of chloroquine and its major bioactive metabolite desethylchloroquine is sparse and incomplete. ⋯ Infant exposure to CQ and DECQ during pregnancy will be similar to that in the maternal circulation, and dependent on maternal dose and frequency. The median CQ + DECQ relative infant dose of 3.2% (as CQ equivalents) was low, confirming that use of CQ during lactation is compatible with breastfeeding.
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Br J Clin Pharmacol · May 2008
Use of a sparse sampling study design to assess transfer of tramadol and its O-desmethyl metabolite into transitional breast milk.
There are presently no published data on tramadol transfer into breast milk or on its effects in the breastfed infant. ⋯ The combined relative infant dose of 2.88% at steady-state was low. The similarity of NACS in exposed infants and controls suggests that there were no significant behavioural adverse effects. We conclude that short-term maternal use of tramadol during establishment of lactation is compatible with breastfeeding.
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Br J Clin Pharmacol · Apr 2008
Randomized Controlled TrialEffect of single doses of maraviroc on the QT/QTc interval in healthy subjects.
To assess the effect of a single dose of maraviroc on the QTc interval in healthy subjects and to evaluate the QTc interval-concentration relationship. ⋯ Single doses of maraviroc, up to and including 900 mg, had no clinically relevant effect on QTcF or QTcI. At all maraviroc doses and for both end-points, the mean difference from placebo for QTc was < 4 ms. There was no apparent relationship between QT interval and maraviroc plasma concentration up to 2363 ng ml(-1). This conclusion held in both male and female subjects, and there was no evidence of a change in the QT/RR relationship with concentration.
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Br J Clin Pharmacol · Apr 2008
Randomized Controlled TrialEffects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers.
To evaluate the influence of cytochrome P450 (CYP) 3A4 inhibitors on the clinical pharmacokinetics of maraviroc, a novel CCR5 antagonist. ⋯ Potent CYP3A4 inhibitors, including ketoconazole and protease inhibitors (except TPV/r), increase maraviroc exposure. Downward adjustment of the maraviroc dose during co-administration with protease inhibitors can compensate for the interaction. TPV/r does not affect the steady-state pharmacokinetics of maraviroc, and hence no dose adjustment would be warranted.
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Br J Clin Pharmacol · Apr 2008
Determinants of chronic benzodiazepine use in the elderly: a longitudinal study.
* The risk of adverse events due to chronic benzodiazepine use is high in the elderly. * Cross-sectional studies have shown that increasing age, female gender and poor physical and mental health are associated with benzodiazepine use. * When users were re-examined some years later, chronic somatic disease, pain and stress seemed to contribute to the continuation of benzodiazepine use. ⋯ The elderly with poor mental and physical health are at an increased risk of chronic benzodiazepine use. Living alone was found to decrease the risk of chronic use, which suggests that social factors may determine drug usage patterns. Very few characteristics predicted chronic benzodiazepine use once patients had received their first prescription. For clinicians, identification of patients at high risk is therefore not straightforward.