Dose linearity after oral administration of tacrolimus 1-mg capsules at doses of 3, 7, and 10 mg.

ABSTRACT

Tacrolimus is an immunosuppressant drug used for the prophylaxis of organ rejection in patients who receive allogenic liver or kidney transplants. This study investigated the relationship between tacrolimus blood concentration-time profiles after 3-, 7-, and 10-mg single oral doses were given to 18 healthy, drug-free, nonsmoking, institutionalized male volunteers. The protocol used a single-dose, 3-period, 3-treatment, nonmasked, randomized-block, complete crossover design. The 90% CIs of the ratios of dose-adjusted, mean, log-transformed values of maximum blood concentration, area under the tacrolimus blood concentration-time curve (0 to the last measurable concentration; lower limit of quantitation = 0.5 ng/mL), and area under the blood concentration-time curve (0 to 0) fell within the range of 125%, indicating dose proportionality for these parameters under experimental conditions. Power to detect a 20% difference for the 3 doses tested was 82.2%, 66.7%, and 72.8%, respectively.