An open-label, two-period, crossover study of the systemic bioavailability in healthy women of clindamycin phosphate from two vaginal cream formulations

R. Saul Levinson, Steven J. Mitan, Jana I. Steinmetz, David J. Gattermeir, Robert J. Schumacher, James L. Joffrion

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Abstract

Background: A clindamycin phosphate 2% single-dose vaginal cream (CSDVC) formulation has been designed to provide release of clindamycin equivalent to 7 daily doses of a conventional clindamycin phosphate 2% vaginal cream (CVC). Objective: The purpose of this study was to comparethe systemic bioavailability of clindamycin from 1 dose of CSDVC with that from 1 dose from a 7-day regimen of CVC in healthy women. Methods: This was a single-center, open-label, randomized, 2-period, 2-sequence crossover study that enrolled healthy, nonpregnant, adult women. Subjects were randomly assigned to receive a single 5-g intravaginal dose of CSDVC or CVC. Blood samples were then collected for 96 hours after study medication administration. Subjects were crossed over after a 14-day washout period, and received a single dose of the other medication. Blood samples were then collected for 96 hours after administration of the second drug. The plasma clindamycin pharmacokinetic profiles were determined, using a validated assay with a lower limit of detection of 0.2 ng/mL, and compared between treatments. Results: The median age of women was 43.5 years(range, 18-66 years), the median weight was 65.0 kg (range, 47.7-91.8 kg), and the median body mass index was 25.4 kg/m2 (range, 19.2-34.7 kg/m2). AUC from time 0 to the last detectable concentration (AUCO0-t) and from time 0 to infinity (AUCO0-∞) and Cmax were significantly lower with CSDVC than with CVC (geometric means of 98.61 vs 794.21 ng·h/mL for AUCO0-t, 100.33 vs 809.14 ng·h/mL for AUC0-∞, and 3.18 vs 42.27 ng/mL for Cmax; all comparisons, P < 0.001 between formulations). Overall bioavailability of clindamycin from CSDVC was ∼12% of that from CVC, as measured by AUC. The arithmetic mean Tmax was significantly longer with CSDVC (26.4 vs 9.8 hours; P < 0.007). There were 18 adverse events reported during this study. The most common adverse event with each formulation was headache (CSDVC, 10%; CVC, 25%). Conclusion: Systemic bioavailability of clindamycinwas significantly lower and systemic absorption was significantly slower with the CSDVC formulation than with the single dose of 7-day CVC formulation in these healthy volunteers.

Original languageEnglish (US)
Pages (from-to)1894-1900
Number of pages7
JournalClinical Therapeutics
Volume27
Issue number12
DOIs
StatePublished - Dec 1 2005

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Keywords

  • Bioadhesive
  • Clindamycin
  • Pharmacokinetics
  • Systemic exposure
  • Vaginal cream
  • Vaginosis

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