HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Correspondence to:

BRIEF COMMUNICATIONS: K. Kompoliti, C. H. Adler, R. Raman, J. H. Pincus, M. T. Leibowitz, J. J. Ferry, L. Blasucci, J. N. Caviness, S. Leurgans, W. M. Chase, L. C. Yones, E. Tan, P. Carvey, and C. G. Goetz Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics Neurology 2002; 58: 1418-1422 [Abstract] [Full text] [PDF]

Correspondence: Submit a response to this article

Correspondence published:

Reply to Letter to the Editor

Katie Kompoliti   (16 August 2002)

Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics

Aldo Quattrone, Mario Zappia   (16 August 2002)

Reply to Letter to the Editor 16 August 2002
Katie Kompoliti Rush-Presbyterian-St. Luke's Medical Center Chicago IL Send Correspondence to journal: Re: Reply to Letter to the Editor kkompoli{at}rush.edu Katie Kompoliti	We fully agree that body weight influences the pharmacokinetics of levodopa in PD. For this reason, and cognizant that women are generally physically smaller and lighter than men, we specifically controlled for body weight and generated our pharmacokinetic curves in units of mg/kg. The gender-based differences in levodopa handling are independent of body weight and require additional research in order to explain the differences between men and women. The role of estrogen is only one avenue of exploration, and the multiple hormonal and biochemical shifts associated with menopause need to be explored in defining the mechanisms underlying our observations and those reported in relationship to gender-based dyskinesia differences. For all pharmacokinetic and pharmacodynamic studies between genders, we suggest careful analytic control of body weight.
Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics 16 August 2002
Aldo Quattrone Facolta di Medicina Catanzaro Italy, Mario Zappia Send Correspondence to journal: Re: Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics quattrone{at}neurol-unicz.it Aldo Quattrone, et al.	We read with interest the article by Kompoliti et al. reporting a gender effect on levodopa (LD) pharmacokinetics. [1] In 26 patients with PD who underwent pharmacokinetic and pharmacodynamic LD evaluation following the administration of a single dose carbidopa/LD 25/100, the authors found that postmenopausal women had a greater LD bioavailability than age-matched men, as evidenced by a higher area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax). They failed to explain the observed gender differences in LD pharmacokinetics, because neither estrogen hormonal status or body weight (AUC was normalized by kilograms of body weight) accounted for these differences. [1] Their results closely mirror the results of our recent study, involving a much larger number of patients with PD (n=164), in which women had higher AUC and Cmax than men following the administration of a single dose carbidopa/LD 25/250. [2] Nevertheless, at variance with the study of Kompoliti et al., we believe that body weight may have a pivotal role in determining the observed gender differences in LD pharmacokinetics, because in our study the body weight was inversely correlated with AUC and women, who were lighter than men, had a greater LUD bioavailability. [2] The discrepancy between our study [2] and theirs may be due to the small sample of patients examined in the latter study, [1] that could have predicted to find out a significant effect of body weight on LD pharmacokinetics. Moreover, in our study women were more dyskinetic than men on the acute LD challenge were and the body weight was inversely correlated with the source of LD-induced dyskinesia. [2] Thus, sex differences occurring in LD pharmacokinetics and related to body weight may explain, at least in part, some LD pharmacodynamic differences, such as the different rate of dyskinesia between women and men. Indeed, since the cumulative LD dose is a well-known risk factor for the development of dyskinesia and in clinical practice LD is administered without any adjustment of the dose to body weight, it could be reasonable to hypothesize that variations in LD pharmacokinetics caused by body weight may expose lighter PD subjects, especially in women, to greater plasma levels during long-term LD therapy and to a greater risk for developing dyskinesia. We agree with the authors’ conclusion suggesting that sex-specific differences in LD bioavailability should be taken into account when dosing women with PD. [1] Furthermore, we would strongly emphasize the relevance of adjusting LD dosage according to body weight for avoiding unwanted side -effects possibly related to a greater LD bioavailability. References: 1)Kompoliti K, Adler CH, Raman R, et al. Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics. Neurology 2002:58:1418-1422. 2)Zappia M, Crescibene L, Arabia G, et al. Body weight influences pharmacokinetics of levodopa in Parkinson’s disease. Clin Neuropharmacol 2002;25:79-82.