Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Aug 2002
Randomized Controlled Trial Clinical TrialPeripheral prostanoid levels and nonsteroidal anti-inflammatory drug analgesia: replicate clinical trials in a tissue injury model.
Nonsteroidal anti-inflammatory drug (NSAID) analgesia is generally attributed to peripheral suppression of cyclooxygenase (COX) enzymes, leading to decreased products of the arachidonic acid cascade. This study evaluated the in vivo relationship between levels of prostanoids at the site of tissue injury and analgesia after systemic or local NSAID administration in a clinical model of tissue injury. ⋯ The temporal profile of PGE(2) and TxB(2) in the immediate postoperative period is consistent with constitutive COX-1 initially, followed by an increase in PGE(2) resulting from expression of COX-2. The temporal association between NSAID analgesia and decreased prostanoids at the site of injury is consistent with a dual COX-1/COX-2 peripheral site of action. The analgesic effects of 1 mg ketorolac tromethamine without a reduction in PGE(2) at the site of injury suggests an additional central site for NSAID analgesia.
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Clin. Pharmacol. Ther. · Aug 2002
Clinical Trial Controlled Clinical TrialPharmacokinetics of valganciclovir and ganciclovir in renal impairment.
Valganciclovir is the oral prodrug of ganciclovir. The pharmacokinetics of valganciclovir in patients with renal impairment is not known. Furthermore, it is not known whether there are any pharmacokinetic differences between patients who are positive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) and healthy subjects. ⋯ The dosage of valganciclovir has to be adjusted to the degree of renal impairment. Dosage adjustment is not necessary for HIV/CMV-positive patients.
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Clin. Pharmacol. Ther. · Aug 2002
Pharmacokinetic modeling to predict morphine and morphine-6-glucuronide plasma concentrations in healthy young volunteers.
This investigation focused on the development of a predictive model of morphine, including morphine-6-glucuronide (M6G) for healthy young volunteers after morphine administration. ⋯ Two models are provided that can predict plasma concentrations of morphine and M6G with acceptable accuracy in healthy young volunteers.