This study explores the hypotheses that: (1) ethanol will interact with dl-Methylphenidate (MPH) to enantioselectively elevate plasma d-MPH, and primarily yield l-ethylphenidate as a transesterification metabolite; (2) women will exhibit lower relative bioavailability of MPH than men; and (3) sex-dependent differences in subjective effects will exist. dl-MPH HCl (0.3 mg/kg) was administered orally 30 min before ethanol, 30 min after ethanol (0.6 gm/kg), or without ethanol, in a randomized, normal subject three-way crossover study of 10 men and 10 women. Pharmacokinetic parameters were compared. Subjective effects were recorded using visual analog scales. One subject was a novel poor MPH metabolizer whose data were analyzed separately. Ethanol after or before MPH significantly (P<0.0001) elevated the geometric mean for the maximum d-MPH plasma concentration (C max (±SD)) from 15.3 (3.37) ng/ml to 21.5 (6.81) and 21.4 (4.86), respectively, and raised the corresponding geometric mean for the area under the concentration-time curve values from 82.9 (21.7) ng ml/h to 105.2 (23.5) and 102.9 (19.2). l-MPH was present in plasma only at 1-3% of the concentration of d-MPH, except in the poor metabolizer where l-MPH exceeded that of d-MPH. The metabolite l-ethylphenidate frequently exceeded 1 ng/ml in plasma, whereas d-ethylphenidate was detected only in low pg/ml concentrations. Women reported a significantly greater stimulant effect than men when questioned "Do you feel any drug effect?" (P<0.05), in spite of lower mean plasma d-MPH area under the response-time curves in women. Ethanol elevates plasma d-MPH C max and area under the concentration-time curve by approximately 40% and 25%, respectively. If the poor metabolizer of MPH proves to be a distinct phenotype, determining the genetic mechanism may be of value for individualizing drug therapy. The more pronounced stimulant effects experienced by women have sex-based abuse liability implications. NIH Public Access Author ManuscriptClin Pharmacol Ther. Author manuscript; available in PMC 2011 October 6. RESULTS Human subjectsTwenty research subjects (10 men aged 23-40 years: mean (±SD) 28.8 (5.3) years, weight 82.2 (10.5) kg, eight white, one black, one Hispanic; and 10 women aged 23-35 years: mean 28.7 (4.4) years, weight 65.2 (8.4) kg, nine white, one black, completed the entire protocol. One additional subject declined further participation after her first visit, citing discomfort with blood sampling. This subject was replaced with another female volunteer to ensure 10 of each sex completed the study. No adverse events occurred that were attributable to MPH, ethanol, or a combination thereof. All vital signs remained within normal parameters. Finally, no subject had any clinically significant findings on poststudy "exit" laboratory tests. (Figure 3). MPH-ethanol pharmacokinetic interactions Sex differences in d-MPH-ethanol pharmacokineticsThe mean (SD) extent of exposure (AUC) of d-MPH was significantly (P=0.042) greater in men (93.4 (25.3) ng h/ml) than i...

Although prior research has identified increases in cigarette smoking following trauma exposure, no studies have examined longitudinal trajectories of smoking following rape. The present investigation identifies and characterizes longitudinal (< 3 months, 3-6 months, and > 6 months post-assault) trajectories of smoking (N = 152) following a rape in a sample of 268 sexual assault victims participating in a forensic medical exam. Further, we examine acute predictors of subsequent smoking trajectories. Of participants endorsing smoking post-rape, a two-class solution was identified, with the majority of participants (74.6%) evidencing moderate smoking with a slight decrease over time and remaining participants showing heavy smoking with a slight increase over time. Having sustained an injury, minority status, and post-exam distress all predicted subsequent smoking trajectory. KeywordsSexual Assault; Rape; Smoking; Cigarettes An estimated 50-70% of individuals in the U.S. experience at least one potentially traumatic event (PTE) during their lifetime (Kessler, Sonnega, Bromet, Hughes, & Nelson, 1995;Kilpatrick et al., 2003). For women, one of the most prevalent PTEs is sexual assault. Over 15 million women (12.6%) in the U.S. are victims of completed rape (Kilpatrick, Edmunds, & Seymour, 1992). In addition to mental health outcomes following traumatic exposure, such as posttraumatic stress disorder (PTSD) and depression, risky health behaviors such as smoking also increase following exposure (Vlahov, Galea, Ahern, Resnick, & Kilpatrick, 2004). Importantly, tobacco use is the most prominent and preventable cause of mortality in the U.S. (Mokdad, Marks, Stroup, & Gerberding, 2004;McGinnis et al., 1993), and therefore is an important public health concern. Although it has been demonstrated that smoking increases post-trauma, little is known about the long-term patterns of behavior, and even less is known about predictors of trajectory. The present study examined longitudinal trajectories of smoking behavior following sexual assault. Given the potential health benefits of early intervention with affected individuals, we examined early predictors of post-assault smoking trajectories. Identification of such predictors may inform understanding of factors that influence posttrauma smoking behaviors and elucidate factors that may facilitate early identification of individuals at risk for sustained increases in smoking. Studies have found a positive relationship between PTE exposure (occurring in childhood or adulthood) and smoking. Two large studies found that experiencing a PTE or adverse life experience in childhood was associated with increased risk of smoking in adulthood (Felitti et al., 1998;Walker et al., 1999). Similar to studies examining childhood exposure to PTEs, sexual assault in adulthood is associated with smoking (Cloutier, Martin, & Poole, 2002). However, these studies were retrospective in nature and are thereby limited by potential recall bias.Recently, longitudinal studies have circumvented this p...