British journal of clinical pharmacology
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Many studies from around the world show a correlation between increasing age and adverse drug reaction (ADR) rate, at least for some medical conditions. More than 80% of ADRs causing admission or occurring in hospital are type A (dose-related) in nature, and thus predictable from the known pharmacology of the drug and therefore potentially avoidable. Frail elderly patients appear to be particularly at risk of ADRs and this group is also likely to be receiving several medicines. ⋯ The use of computer-based decision support systems (CDSS) and electronic prescribing should be encouraged, and when problems do occur, health professionals need to be aware of their professional responsibility to report suspected adverse drug events (ADEs) and ADRs. "Rational" or "obligatory" polypharmacy is becoming a legitimate practice as increasing numbers of individuals live longer and the range of available therapeutic options for many medical conditions increases. The clear risk of ADRs in this situation should be considered in the context that dose-related failure of existing therapy to manage the condition adequately may be one of the most important reasons for admission of the elderly to hospital. Thus, age itself should not be used as a reason for withholding adequate doses of effective therapies.
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Br J Clin Pharmacol · Dec 2003
Randomized Controlled Trial Clinical TrialNo clinically significant pharmacokinetic interactions between voriconazole and indinavir in healthy volunteers.
Voriconazole is a new triazole antifungal agent, and is metabolized by the cytochrome P450 isoenzymes CYP2C9, CYP2C19 and to a lesser extent by CYP3A4. Protease inhibitors, such as indinavir, are also metabolized by cytochrome P450 (mainly CYP3A4). As these drugs are likely to be coadministered, these studies were performed to assess the pharmacokinetic interactions, safety and toleration of these drugs when taken together. ⋯ The coadministration of voriconazole and indinavir in healthy volunteers had no clinically significant effect on the pharmacokinetics of either voriconazole or indinavir.
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Br J Clin Pharmacol · Aug 2003
Randomized Controlled Trial Clinical TrialA simple pain model for the evaluation of analgesic effects of NSAIDs in healthy subjects.
Non-steroidal anti-inflammatory drugs (NSAIDs) are believed to counteract inflammation and inflammation-induced sensitization of nociceptors by inhibiting peripheral prostaglandin synthesis. We evaluated an experimental pain model for NSAIDs, that included an inflammatory component to mimic clinical inflammatory pain conditions. ⋯ The pain model we evaluated was well tolerated in all subjects and the effects of ibuprofen were highly significant. This model is simple, sensitive to NSAIDs' effects and therefore has potential for future experimental pain studies.
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Br J Clin Pharmacol · Jul 2003
Antibiotic prescribing for children. Too much and too little? Retrospective observational study in primary care.
To investigate the extent of dose-related off-label antibiotic paediatric prescribing in primary care and to identify any potential clinical effects, particularly of lower than recommended dose prescribing. ⋯ Off-label prescribing of antibiotics at less than the recommended dose in children is common in primary care and occurs primarily as the result of a failure to increase antibiotic dosage with age in line with SPC recommendations. Adoption of a uniform approach to SPC age banding for antibiotic dose increments would reduce the frequency of dose-related off-label antibiotic prescribing in children and help minimize the potential for the development of antibiotic resistance.
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Br J Clin Pharmacol · Jul 2003
Pharmacokinetics and clinical effects of phenytoin and fosphenytoin in children with severe malaria and status epilepticus.
Status epilepticus is common in children with severe falciparum malaria and is associated with poor outcome. Phenytoin is often used to control status epilepticus, but its water-soluble prodrug, fosphenytoin, may be more useful as it is easier to administer. We studied the pharmacokinetics and clinical effects of phenytoin and fosphenytoin sodium in children with severe falciparum malaria and status epilepticus. ⋯ Phenytoin and fosphenytoin administration at the currently recommended doses achieve plasma unbound phenytoin concentrations within the therapeutic range with few cardiovascular effects. Administration of fosphenytoin i.v. or i.m. offers a practical and convenient alternative to i.v. phenytoin. However, the inadequate control of status epilepticus despite rapid achievement of therapeutic unbound phenytoin concentrations warrants further investigation.