BOOTSTRAP CONFIDENCE INTERVAL APPROACH TO COMPARE BIOAVAILABILITY OF ORAL LEVODOPA CARBIDOPA TABLET VS INTRANASAL LEVODOPA MICROSPHERES

V. Chandrakala*, A Mary Saral, Utpalkumar Sanki

ABSTRACT

Aim of the present study is pharmacokinetic comparison between nasal levodopa carbidopa formulation, nasal levodopa microspheres (test) and oral levodopa carbidopa tablet in rat. The comparative pharmacokinetic study was carried out on 324 healthy experimental rats in an open label randomized, parallel, three treatment, serial sacrifice design in 54 groups. All PK parameters were calculated using a noncompartmental model. The mean AUCt for each product and time point t of measurement is calculated by using the mean concentrations (Ct) at each time point t to derive the mean profile for each product. The ratio and 90%CI for nasal l-dopa/nasal ldopa+ c-dopa formulation was 96.94(60.05-133.83) for Cmax and 92.29(66.54-118.04) for AUCt. Despite 90% CI limit not within the bioequivalence limit of 80% to 125% both formulation are equivalent at ratio test. Since animal sample size were less, 90% CI could not be met otherwise expected to meet at higher number of animal. The above statement is further proved by student t-test as probability of detecting difference between above formulations, at 95% CI was 0.547 which signifies there is no significant difference between two formulations. Since the value were not within the limit of 80-125% the test and reference product were pharmacokinetic nonequivalence and indicated that that this comparative pharmacokinetic study was well designed to conclude that the test formulation and reference formulation were pharmacokinetically non equivalent. Based on the above analysis it was found that nasal microspheres of levodopa were suprabioavailable compared to oral.

Keywords: Parkinson’s disease, nasal microspheres, bootstrap, l-dopa, pharmacokinetics.