The pharmacokinetics and pharmacodynamics of the intravenous (IV) formulation and oral (PO) (extended release) formulation of morphine will be determined in this randomized cross-over 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 wash-out period of not less than seven 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 following PO morphine administration, and will be assessed 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 co-modeled with the pharmacodynamic data and statistical comparisons will be made between groups. Preliminary experience based on 4NV and 3 SCA patients suggest that SCA patients may be a higher pain threshold both before and after PO morphine administration. 12 subjects have completed both trial phases. The pharmacokinetics and pharmacodynamics have not been formally analyzed.
