Bioavailability testing of a newly developed clindamycin oral suspension in a pediatric porcine model

Pharm Dev Technol. 2019 Oct;24(8):1038-1043. doi: 10.1080/10837450.2019.1624771. Epub 2019 Jun 21.

Abstract

Background: Clindamycin's bitter taste and odor is known to affect treatment adherence in children. Recently, a formulation of clindamycin HCl complexed with ion exchange resin IRP 69 was shown to mask the bitter taste. Because of the potential benefit of this formulation for children, a pilot study using a porcine model was conducted to evaluate its relative bioavailability. Methods: A randomized two-way crossover study design using six (n = 6) healthy male piglets 10-12 kg was used to evaluate the absorption profiles and pharmacokinetic parameters of clindamycin from the resinate complex formulation (Test) compared to a commercialized reference suspension. A dose of 15 mg/kg was administered orally by gastric gavage to each piglet followed by repeated blood sampling over 12 h. A wash-out period of 48 h occurred between treatments. Plasma concentration vs. time data was analyzed by non-compartmental analysis. Results: The mean relative bioavailability of clindamycin from the resinate formulation was 78.8%. A two-tailed, paired Student t test yielded a p < 0.05 for AUC and Tmax parameters. A two one-sided test (TOST) suggested a difference in AUC and Cmax for the Test formulation compared to the reference formulation according to the FDA's criteria for bioequivalence. Conclusion: The bioavailability of clindamycin from this novel oral formulation supports continued evaluation of the drug in humans for potential pediatric applications.

Keywords: Amberlite IRP 69; bioequivalent; clindamycin; ion exchange resin; pediatric formulations; pharmacokinetics; piglet; taste masking.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / pharmacokinetics
  • Area Under Curve
  • Biological Availability
  • Clindamycin* / administration & dosage
  • Clindamycin* / pharmacokinetics
  • Cross-Over Studies
  • Half-Life
  • Ion Exchange Resins* / pharmacokinetics
  • Male
  • Pilot Projects
  • Suspensions
  • Swine
  • Taste* / drug effects
  • Therapeutic Equivalency

Substances

  • Anti-Bacterial Agents
  • Clindamycin
  • Ion Exchange Resins
  • Suspensions