Pregabalin and gabapentin share a similar mechanism of action, inhibiting calcium influx and subsequent release of excitatory neurotransmitters; however, the compounds differ in their pharmacokinetic and pharmacodynamic characteristics. Gabapentin is absorbed slowly after oral administration, with maximum plasma concentrations attained within 3-4 hours. Orally administered gabapentin exhibits saturable absorption--a nonlinear (zero-order) process--making its pharmacokinetics less predictable. Plasma concentrations of gabapentin do not increase proportionally with increasing dose. In contrast, orally administered pregabalin is absorbed more rapidly, with maximum plasma concentrations attained within 1 hour. Absorption is linear (first order), with plasma concentrations increasing proportionately with increasing dose. The absolute bioavailability of gabapentin drops from 60% to 33% as the dosage increases from 900 to 3600 mg/day, while the absolute bioavailability of pregabalin remains at > or = 90% irrespective of the dosage. Both drugs can be given without regard to meals. Neither drug binds to plasma proteins. Neither drug is metabolized by nor inhibits hepatic enzymes that are responsible for the metabolism of other drugs. Both drugs are excreted renally, with elimination half-lives of approximately 6 hours. Pregabalin and gabapentin both show dose-response relationships in the treatment of postherpetic neuralgia and partial seizures. For neuropathic pain, a pregabalin dosage of 450 mg/day appears to reduce pain comparably to the predicted maximum effect of gabapentin. As an antiepileptic, pregabalin may be more effective than gabapentin, on the basis of the magnitude of the reduction in the seizure frequency. In conclusion, pregabalin appears to have some distinct pharmacokinetic advantages over gabapentin that may translate into an improved pharmacodynamic effect.

The low productivity and escalating costs of drug development have been well documented over the past several years. Less than 10% of new compounds that enter clinical trials ultimately make it to the market, and many more fail in the preclinical stages of development. These challenges in the "critical path" of drug development are discussed in a 2004 publication by the US Food and Drug Administration. The document emphasizes new tools and various opportunities to improve drug development. One of the opportunities recommended is the application of "model-based drug development (MBDD)." This paper discusses what constitutes the key elements of MBDD and how these elements should fit together to inform drug development strategy and decision-making.

Physical activity has been associated with a reduced risk of gestational diabetes mellitus, but inferences have been hampered by recall and selection bias. The authors examined the relation between recreational physical activity before and during pregnancy and risk of gestational diabetes mellitus in a prospective cohort study. In 1996-2000, 909 normotensive, nondiabetic women in Seattle and Tacoma, Washington, were questioned during early gestation about physical activity performed during the year before and 7 days prior to the interview during pregnancy. Compared with inactive women, women who participated in any physical activity during the year before experienced a 56% risk reduction (relative risk (RR) = 0.44, 95% confidence interval (CI): 0.21, 0.91). Women spending >/=4.2 hours/week engaged in physical activity experienced a 76% reduction in gestational diabetes mellitus risk (RR = 0.24, 95% CI: 0.10, 0.64), and those expending >/=21.1 metabolic equivalent-hours/week experienced a 74% reduction (RR = 0.26, 95% CI: 0.10, 0.65) compared with inactive women. Physical activity during pregnancy was also associated with reductions in gestational diabetes mellitus risk. Women who engaged in physical activity during both time periods experienced a 69% reduced risk (RR = 0.31, 95% CI: 0.12, 0.79). Findings suggest that efforts to increase maternal physical activity may contribute to substantial reductions in gestational diabetes mellitus risk.

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Early pregnancy dyslipidemia is associated with an increased risk of preeclampsia. This association may be significant in understanding the pathologic processes of preeclampsia and may help in developing strategies for prevention or early diagnosis of the disorder.

A disease progression model adequately described the natural decline of ADAS-cog observed in Alzheimer's Disease Neuroimaging Initiative. Baseline severity is an important covariate to predict a curvilinear rate of disease progression in normal elderly, mild cognitive impairment, and AD patients. Age, APOE ɛ4 genotype, and gender also influence the rate of disease progression.

Our findings are consistent with a larger literature that documents elevated blood pressure and increased risks of hypertension with short and long sleep duration.

Objective: To evaluate associations between early pregnancy 25-hydroxyvitamin D (25[OH]D) concentrations and antepartum depression and anxiety symptoms and potential modifiers thereof. Materials and Methods: In a pregnancy cohort (N = 498), we examined cross-sectional associations of early pregnancy (mean = 15.4 weeks gestation) serum 25[OH]D concentrations and depression and anxiety symptoms. Symptoms were measured using Depression, Anxiety, and Stress Scales (DASS-21) and Patient Health Questionnaire Depression Module (PHQ-9) instruments. Regression models were fit and effect modification by prepregnancy body mass index and leisure-time physical activity (LTPA) were assessed using interaction terms and stratified analyses. ( < 28.9 ng/mL) had 1.11 higher PHQ-9 scores than those in the highest quartile ( ‡ 39.5 ng/mL, p < 0.05). However, associations were attenuated and statistically insignificant in fully adjusted models. Inverse associations of 25[OH]D with depression symptoms were significant among participants who reported no LTPA, but not among women who reported any LTPA (interaction p = 0.018). Conclusions: Our study provides modest evidence for inverse cross-sectional associations of early pregnancy maternal vitamin D concentrations with antepartum depression symptoms. We also observed that these associations may be modified by physical activity.