Pregabalin has shown clinical efficacy for treatment of neuropathic pain syndromes, partial seizures, and anxiety disorders. Five studies in healthy volunteers are performed to investigate single- and multiple-dose pharmacokinetics of pregabalin. Pregabalin is rapidly absorbed following oral administration, with peak plasma concentrations occurring between 0.7 and 1.3 hours. Pregabalin oral bioavailability is approximately 90% and is independent of dose and frequency of administration. Food reduces the rate of pregabalin absorption, resulting in lower and delayed maximum plasma concentrations, yet the extent of drug absorption is unaffected, suggesting that pregabalin may be administered without regard to meals. Pregabalin elimination half-life is approximately 6 hours and steady state is achieved within 1 to 2 days of repeated administration. Corrected for oral bioavailability, pregabalin plasma clearance is essentially equivalent to renal clearance, indicating that pregabalin undergoes negligible nonrenal elimination. Pregabalin demonstrates desirable, predictable pharmacokinetic properties that suggest ease of use. Because pregabalin is eliminated renally, renal function affects its pharmacokinetics.

No abstract

Tolerance and pharmacokinetics after single-dose administration of atorvastatin, an investigational inhibitor of HMG-CoA reductase, were examined in 22 healthy volunteers in a three-period, partially-blinded study. Participants received capsule and solution doses of atorvastatin (0.5 to 120 mg) and placebo at weekly intervals. Atorvastatin was well tolerated at doses as high as 80 mg. The adverse event profile was similar after administration of atorvastatin capsules and placebo. Atorvastatin solution was slightly less well tolerated. The most common side effect after administration of capsules and solution was headache, followed by sporadic reports of diarrhea, flatulence, and nausea. At the 120-mg solution dose, one participant experienced mild, transient restlessness, euphoria, and mental confusion that were considered to be dose-limiting side effects. Mean concentrations of atorvastatin, maximum concentration (Cmax), and area under the concentration-time curve from time 0 to the time of the last detectable concentration (AUCo-tldc) increased with increasing dose. Plasma elimination half-life (t1/2) ranged from 14.7 to 57.6 hours. The bioavailability of atorvastatin capsules was similar to that of solution. These results suggest that atorvastatin is well tolerated after single doses as high as 80 mg, and may require administration only once daily.

No abstract

To determine whether atorvastatin, a new HMG-CoA reductase inhibitor, could be administered with food in Phase II and III clinical trials, a nonblind, randomized, two-way crossover study was conducted to assess the effect of food on rate and extent of atorvastatin absorption. Sixteen healthy volunteers received single 80-mg atorvastatin capsule doses on two occasions one week apart: once after an 8-hour overnight fast and once with a medium-fat breakfast. The single 80-mg atorvastatin capsule doses were well-tolerated. Mean maximum plasma atorvastatin equivalent concentration (Cmax) and area under the concentration-time curve (AUC) values with food were 47.9% and 12.7% lower, respectively, than without food. Mean time of maximum observed concentration (tmax) and elimination half-life (t1/2) values were 5.9 and 32.0 hours, respectively, with food and 2.6 and 35.7 hours, respectively, without food. A medium-fat breakfast decreased the rate of atorvastatin absorption significantly, but had little impact on extent of drug absorption. Changes in rate of atorvastatin absorption are not expected to have a clinically significant effect, as subsequent multiple-dose clinical studies have shown that dose but not plasma atorvastatin concentration profiles correlates with lipid-lowering effects.