The pharmacokinetics and pharmacodynamics of the intravenous (IV) formulation and oral (PO) (extended-release) formulation of morphine will be determined in this randomized crossover study. Twelve patients with sickle cell anemia (SCA) and 12 normal volunteers (NV) matched by age, sex, and race will be enrolled. There will be a washout period of not less than 7 days between either PO and IV drug administration. Pharmacokinetic parameters (Cmax, Tmax, Kel.T1/2, AUC, Vd, F) will be calculated for morphine and its two primary metabolites for PO and IV administration. Pharmacodynamics will be assessed prior to 2.5 and 5 hours after PO morphine is administered, using an experimental pain model (thermal sensitivity testing). Determination of pain threshold will be used to evaluate pharmacodynamic response to morphine. Pharmacokinetic parameters will be comodeled with the pharmacodynamic data, and statistical comparisons will be made between groups. Preliminary experience based on four NV and three SCA patients suggests that SCA patients may have a higher pain threshold both before and after PO morphine administration. Twelve subjects have completed both trial phases. The pharmacokinetics and pharmacodynamics have not been formally analyzed.
