We measured the pharmacokinetics of hydromorphone in normal volunteers given three doses of the drug (10, 20, and 40 μg/kg) as intravenous 45-s injections on different days. Concentrations of hydromorphone in plasma from serial blood samples were measured by a high-performance liquid chromatography method specific for hydromorphone with a detection limit of 0.1 ng/mL. In all cases, plasma hydromorphone concentration versus time data for individual subjects were best described by a triexponential (instead of mono- or biexponential) function. Furthermore, we found that the pharmacokinetics of hydromorphone was independent of dose across the range studied. Averaged across doses, the distribution and terminal elimination half-lives were 1.27 min (t1/2π), 14.7 min (t1/2α), and 184 min (t1/2β), respectively. Average values for systemic clearance, initial dilution volume, and steady-state volume of distribution were 1.66 L/min (Cl), 24.4 L (Vc), and 295 L (Vdss). Our results indicate that hydromorphone pharmacokinetic parameters are linear across a fourfold range of doses that are usually employed clinically and that previously reported pharmacokinetic values for hydromorphone (based on radioimmunoassay measurements) deserve reconsideration.
Address correspondence to Dr. Hill, Pain and Toxicity Research Program, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA 98104.
© 1991 International Anesthesia Research Society