Journal of clinical pharmacology
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Randomized Controlled Trial Comparative Study Controlled Clinical Trial
Pharmacokinetics of gabapentin in a novel gastric-retentive extended-release formulation: comparison with an immediate-release formulation and effect of dose escalation and food.
The objectives of the 3 phase I studies described herein were (1) to compare the pharmacokinetics of gabapentin delivered from a novel gastric-retentive dosage form vs an immediate-release formulation, (2) to assess the dose proportionality of the gastric-retentive extended-release formulation, and (3) to determine the effect of food on the pharmacokinetics of gabapentin delivered from this formulation. The time to reach maximum plasma concentration (t(max)) was extended for gabapentin delivered from the gastric-retentive extended-release formulation compared with the immediate-release formulation. ⋯ Fed status and increased fat content delayed t(max) and enhanced C(max) and AUC in proportion to the fat content. The pharmacokinetics of gabapentin delivered from this extended-release formulation allows a reduced dosing frequency while maintaining bioavailability and possibly diminishing the occurrence of adverse events attributable to a slower increase to the peak concentration compared with the immediate-release dosage form.
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Hypovolemia from a range of etiologies can lead to severe morbidity and mortality unless blood volume and tissue perfusion are restored. The treatment of hypovolemia has included the improvement and restoration of blood volume loss by the intravenous infusion of plasma expanding therapeutic agents. These have included crystalloid and/or colloid solutions, and a brisk controversy as to which modality is better has engaged therapeutics for the past 30 years. ⋯ This area was given a dramatic turn a decade ago when a Cochrane meta-analysis concluded that albumin, a historically important plasma expander, resulted in increased mortality when administered to critically ill patients. Although subsequently modified by other studies, the Cochrane meta-analysis has served to generate an ongoing interest in the safety of plasma expanders. This review will assess the safety of these therapies from the viewpoint of the heterogeneous range of clinical indications for which they are used.
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Controlled Clinical Trial
Influence of severe renal impairment on the pharmacokinetics of clazosentan.
The purpose of this open-label, parallel-group study was to investigate the effect of severe renal impairment on the pharmacokinetics (PK), tolerability, and safety of clazosentan, an intravenous endothelin receptor antagonist. Clazosentan was administered as a continuous intravenous infusion of 1 mg/h for a period of 6 hours in 9 subjects with severe renal impairment (group A) and 8 healthy subjects (group B) (creatinine clearance <30 mL/min and >80 mL/min, respectively). The subjects in both groups were well matched for sex, body mass index, and age (±10 years). ⋯ The results obtained after 2-compartmental modeling were in agreement with those obtained after noncompartmental analysis. Administration of clazosentan was well tolerated in both groups. The data suggest that there is no need for dose adjustment of clazosentan in patients with renal impairment.