title: An open-label, two-period, crossover study of the systemic bioavailability in healthy women of clindamycin phosphate from two vaginal cream formulations.
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 compare the 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/m(2)). AUC from time 0 to the last detectable concentration (AUCO(0-t)) and from time 0 to infinity (AUCO(0-infinity)) and C(max) were significantly lower with CSDVC than with CVC (geometric means of 98.61 vs 794.21 ng . h/mL for AUCO(0-t), 100.33 vs 809.14 ng . h/mL for AUC(0-infinity), and 3.18 vs 42.27 ng/mL for C(max); all comparisons, P < 0.001 between formulations). Overall bioavailability of clindamycin from CSDVC was approximately 12% of that from CVC, as measured by AUC. The arithmetic mean T(max) 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%).
  
  
  CONCLUSIONS
  Systemic bioavailability of clindamycin was 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.
authors.affiliation: KV Pharmaceutical Company, St. Louis, MO 63144, USA.
authors.forename: R Saul
authors.initials: RS
authors.lastname: Levinson
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Mitan
authors.forename: Jana I
authors.initials: JI
authors.lastname: Steinmetz
authors.forename: David J
authors.initials: DJ
authors.lastname: Gattermeir
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schumacher
authors.forename: James L
authors.initials: JL
authors.lastname: Joffrion
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002981:Clindamycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014622:Vaginal Creams, Foams, and Jellies; D002981:Clindamycin; C007084:clindamycin phosphate