PHARMACOKINETIC AND SAFETY EVALUATIONS OF KETOPROFEN GELS IN SUBJECTSWITH ADULT PERIODONTITIS

This clinical trial used a randomized, partially double-blind, control led parallel design to evaluate the pharmacokinetics and safety of the NSAID, ketoprofen (KTP), in gel formulations. Forty-two subjects, age s 35 to 57 years, with generalized, moderate to advanced adult periodo ntitis were recruited and randomized to one of 5 treatments over a 14 1/2-day treatment period: (1) 0.5% KTP gel; (2) 1.0% KTP gel; (3) 1.0% KTP alternate gel; (4) 2.0% KTP gel; and (5) 25 mg KTP capsule (posit ive control). Plasma samples were obtained on days 1 (pre-dosing, 0.5, 1, 2, 3, 6 hr), 8 (pre-dosing, 2 hr), 15 (pre-dosing, 2 hr), and 22 ( 7 days post-treatment). Plasma KTP concentrations were determined by m eans of high-performance liquid chromatography. Significant difference s in mean area under the plasma concentration vs, time curve (AUC(0-in finity)) among the groups were detected (p < 0.001), with the 25 mg p. o. capsule exhibiting the largest value (5054 ng-hr/mL), the 2.0% gel exhibiting an intermediate value (2244 ng-hr/mL), the 1.0% gels exhibi ting lower but comparable values (1516 for the alternate formulation v s. 1461 ng-hr/mL), and the 0.5% gel showing the lowest value (736 ng-h r/mL). Significant differences in dose- and weight-adjusted maximum pl asma concentration (C-max/dose/kg) were detected overall such that the 25 mg p.o. capsule demonstrated higher values as compared with the 4 gel formulations (p = 0.001). The 5 treatments exhibited similar mean times of maximum plasma concentration (t(max)) values ranging from 0.6 to 1 hr. Systemic exposures relative to dose and body weight were low er for the gel formulations than for the capsule. The relative systemi c bioavailability of the gels compared with peroral administration ran ged from 54% to 69%.