Adapalene pretreatment increases follicular penetration of clindamycin: in vitro and in vivo studies.

BACKGROUND: Topical retinoids normalize desquamation, reduce comedogenesis and may enhance the penetration of other topicals providing more effective treatment of acne. AIM: We evaluated the effect of adapalene on skin penetration of clindamycin phosphate when it is applied concomitantly or after various time durations following adapalene application. METHODS: The in vitro studies were carried out using excised rat skin, whereas the in vivo studies were conducted on healthy human volunteers. Radioactive clindamycin phosphate (1%) gel was applied to rat skin sections and to the hands of human volunteers concomitantly and after the pretreatment of the skin for 3, 5 and 10 min with 10 mg of adapalene (0.1%) gel. Quantification of clindamycin phosphate was performed by liquid scintillation. RESULTS: In vitro skin penetration and distribution of clindamycin phosphate was affected by the pretreatment time. Significantly higher skin concentration of clindamycin phosphate (15.5%) with largest proportion in viable skin layer (9.4% of applied dose) was found when clindamycin phosphate gel was applied after the pretreatment of the skin with adapalene gel for 5 min. Further increase in pretreatment time has no additive influence on the penetration of clindamycin phosphate. In vivo results were in corroboration with the in vitro results and demonstrate significantly higher concentration of clindamycin phosphate (19%) in the skin following pretreatment with adapalene gel for 5 min. Adapalene acts as a penetration enhancer and increases the penetration of topical clindamycin phosphate. CONCLUSION: Application of clindamycin phosphate gel after the pretreatment of skin with adapalene gel for 5 min may contribute significantly to the increased efficacy of therapy.

Bioequivalence study of clindamycin phosphate injection (Clinott-P) in Thai healthy volunteers.

BACKGROUND AND OBJECTIVE: Generic clindamycin given intramuscularly, should have identical active ingredient(s), strength, and demonstrable bioequivalence to those of original product. The aim of this investigation was to compare the bioavailability of a single, intramuscular injection, of 2 ml. of 300 mg. of a generic clindamycin (Clinott-P) and the original preparation (Dalacin C). MATERIAL AND METHOD: A randomized, double-blinded, crossover study was conducted. Twenty-four healthy males were recruited at Siriraj Hospital and randomized to receive a single intramuscular injection of either Clinott-P or Dalacin C. Treatment was followed by a two-week washout period. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours after the injection. Plasma samples were analysed for clindamycin by a validated HPLC method at the Faculty of Pharmaceutical Sciences, Chulalongkorn University. RESULTS: Twenty-four volunteers enrolled in and completed the study. They exhibited an average height of 167.92 cm (SD = 5.82), weight of 60.10 kg (SD = 7.36), body mass index of 21.27 (SD = 1.73) and normal blood chemistries. The Cmax of Clinott-P was 3.94225 microg/ml at Tmax 1.75 hours and of Dalacin C, 3.6847 microg/ ml at Tmax 2.09 hours. The AUC0-24 of Clinott-P was 16.32 +/- 6.13 micro.hr/ml and Dalacin C was 17.24 +/- 7.46 microg.hr/ml. Ninety percent confidence intervals of the mean ratios (test/reference) of log transformed of Cmax (93.07-123.43%), AUC(0-24) (82.58-112.31%) and AUC(0-inf), (81.54-110.06%) were all within the standard range (80-125 %) for bioequivalence study. Tenderness after injection around the deltoid area was assessed blindly and was found to be slight (visual basic score < 5) and presented for one or two days after the injection. CONCLUSION: The two brands of clindamycin exhibit comparable pharmacokinetic parameters and volunteers exhibited slight and tolerable tenderness at the injection site.