Clin Pharmacokinet
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Antimicrobials are among the most important and commonly prescribed drugs in the management of critically ill patients. Selecting the appropriate antimicrobial at the commencement of therapy, both in terms of spectrum of activity and dose and frequency of administration according to concentration or time dependency, is mandatory in this setting. Despite appropriate standard dosage regimens, failure of the antimicrobial treatment may occur because of the inability of the antimicrobial to achieve adequate concentrations at the infection site through alterations in its pharmacokinetics due to underlying pathophysiological conditions. ⋯ On the other hand, overexposure may occur because of a drop in renal clearance caused by renal impairment. Care with all these factors whenever choosing an antimicrobial may substantially improve the outcome of antimicrobial therapy in critically ill patients. However, since these situations may often coexist in the same patient and pharmacokinetic variability may be unpredictable, the antimicrobial policy may further benefit from real-time application of therapeutic drug monitoring, since this practice, by tailoring exposure to the individual patient, may consequently be helpful both in improving the outcome of antimicrobial therapy and in containing the spread of resistance in the hospital setting.
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Randomized Controlled Trial Clinical Trial
Pharmacokinetic evaluation of meropenem and imipenem in critically ill patients with sepsis.
To evaluate and compare the pharmacokinetic profiles of imipenem and meropenem in a population of critically ill patients with sepsis to find possible differences that may help in selecting the most appropriate drug and/or dosage in order to optimise empiric antimicrobial therapy. ⋯ The more favourable pharmacokinetic profile of imipenem compared with meropenem in critically ill patients with sepsis might balance the possibly greater potency demonstrated in vitro for meropenem against Gram-negative strains. Hence, the clinical efficacy of the two carbapenems depends mostly on their correct dosage.
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Randomized Controlled Trial Clinical Trial
Contribution of cytochrome P450 2D6 to 3,4-methylenedioxymethamphetamine disposition in humans: use of paroxetine as a metabolic inhibitor probe.
3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative typically used for recreational purposes. The participation of cytochrome P450 (CYP) 2D6 in the oxidative metabolism of MDMA may suggest an increased risk of acute toxicity in CYP2D6 poor metabolisers. This study was aimed at assessing the contribution of CYP2D6 to MDMA disposition in vivo using paroxetine as a metabolic probe inhibitor. Paroxetine, a CYP2D6 inhibitor, was repeatedly administered before MDMA administration. ⋯ The contribution of CYP2D6 to MDMA metabolism in humans is not >30%, therefore other CYP isoenzymes may contribute to O-demethylenation of MDMA. Accordingly, the relevance of genetic polymorphism in CYP2D6 activity on MDMA effects and MDMA-induced acute toxicity should be examined as well as the interactions of other CYP2D6 substrates with MDMA, once the enzyme is inhibited. The pharmacokinetics of HM-paroxetine in humans after the administration of repeated doses is reported for the first time in this study.
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Randomized Controlled Trial Clinical Trial
The effect of dosing frequency on the pharmacokinetics of a fentanyl HCl patient-controlled transdermal system (PCTS).
The fentanyl HCl patient-controlled transdermal system (PCTS) is a noninvasive, needle-free, credit card-sized drug delivery system designed for the on-demand management of acute pain in a medically supervised setting. The objective of these studies was to determine the effect of dosing frequency on the pharmacokinetics of fentanyl delivered by the PCTS. ⋯ The amount of fentanyl absorbed from the PCTS increases as a function of time and is independent of both dosing frequency and total number of doses delivered. The fentanyl HCl PCTS is generally safe and well tolerated.
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Randomized Controlled Trial Clinical Trial
Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients.
Valganciclovir (Valcyte) has recently been approved for the prevention of cytomegalovirus (CMV) disease in high-risk (CMV donor positive [D+]/recipient negative [R-]) solid organ transplant (SOT) recipients. Large-scale studies describing the pharmacokinetics of valganciclovir in SOT recipients are lacking. A recent randomised, double-blind study of valganciclovir in 364 D+/R- (intent-to-treat population) SOT recipients provided valuable data on which a population pharmacokinetic analysis was performed. ⋯ Oral valganciclovir produces exposures of ganciclovir exceeding those attained with oral ganciclovir, but in line with those reported after standard intravenous administration of ganciclovir. This indicates that oral valganciclovir is suitable in circumstances requiring prophylactic use of ganciclovir and allows for more convenient management of patients at risk of CMV disease.