Bioequivalence of oral and intravenous carbamazepine formulations in adult patients with epilepsy
| Autor: | Rebecca Drummond, Victor Biton, David L. Wesche, James C. Cloyd, Ihor Bekersky, Dwain Tolbert, Mark Walzer, Deborah Lee |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Time Factors Drug-Related Side Effects and Adverse Reactions Cmax Administration Oral Pharmacokinetic Bioequivalence Cmin Young Adult Pharmacokinetics Oral administration medicine Humans Cyclodextrin Infusions Intravenous Aged Full-Length Original Research Epilepsy business.industry Carbamazepine Middle Aged Treatment Outcome Neurology Tolerability Anesthesia Area Under Curve Anticonvulsants Female Neurology (clinical) business Intravenous carbamazepine medicine.drug Blood sampling Follow-Up Studies |
| Zdroj: | Epilepsia |
| ISSN: | 1528-1167 |
| Popis: | Summary Objective To evaluate the safety, tolerability, and comparative pharmacokinetics (PK) of intravenous and oral carbamazepine. Methods In this phase 1, open-label study, adult patients with epilepsy on a stable oral carbamazepine dosage (400–2,000 mg/day) were converted to intravenous carbamazepine (administered at 70% of the oral dosage). A 28-day outpatient period preceded an up to 10-day inpatient period and a 30-day follow-up period. Intravenous carbamazepine was administered over 15 or 30 min every 6 h on days 1–7; some patients in the 15-min group were eligible to receive four 2- to 5-min (rapid) infusions on day 8. Patients underwent blood sampling to determine the area under the concentration–time curve (AUC) for carbamazepine and metabolite carbamazepine-10,11-epoxide following oral (day 0) and intravenous carbamazepine administration (days 1, 7, and 8). Bioequivalence was evaluated in patients with normal renal function (creatinine clearance >80 ml/min). Safety assessments were conducted through day 38. Results Ninety-eight patients enrolled and 77 completed the PK component. The mean daily oral and intravenous carbamazepine dosage for 64 PK-evaluable patients with normal renal function was 962.5 and 675.1 mg (70% of oral dosage), respectively. Steady-state minimum concentration (Cmin) and overall exposure (AUC0–24) for intravenous carbamazepine infused over 30, 15, or 2–5 min were similar to oral carbamazepine. The 90% confidence intervals (CIs) for the ratios of the adjusted means for AUC0–24, maximum concentration (Cmax), and Cmin were within the 80%–125% bioequivalence range for 30-min intravenous infusions versus oral administration, but exceeded the upper limit for Cmax for the 15-min and rapid infusions. All intravenous carbamazepine infusions were well tolerated. Significance Intravenous carbamazepine infusions (70% of oral daily dose) of 30-, 15-, and 2- to 5-min duration, given every 6 h, maintained patients’ plasma carbamazepine concentrations. Intravenous carbamazepine 30-min infusions were bioequivalent to oral carbamazepine in patients with normal renal function; rapid infusions were well-tolerated in this study. |
| Databáze: | OpenAIRE |
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