Pharmacodynamics of Orally Administered Sustained- release Hydromorphone in Humans

Abstract

A single oral dose of a new sustained-release formulation of hydromorphone provided analgesia to experimental pain beyond 24 h of its administration.

Metabolic activation and analgesic effect of flupirtine in healthy subjects, influence of the polymorphic NAT2, UGT1A1 and GSTP1

“…Each pain tolerance value was the median of five subsequent measurements obtained at intervals of 1 min. This pain model has been demonstrated previously to be suitable for quantifying analgesic effects of strong opioids [32][33][34][35].…”

Teaching From Catastrophe: Using Therapeutic Misadventures From Hydromorphone to Teach Key Principles in Clinical Pharmacology

“…29 This issue is not unique to hydromorphone but is shared with other hydrophilic opioids (eg, morphine with its combined transfer half-life of 10 hours, with its active morphine 6-glucuronide metabolite). 17 In contrast, the lipophilic opioids have far shorter transfer half-lives (fentanyl, 5 minutes), …”

“…In addition, patient 4 once again underscores the problem with accumulation of the hydromorphone in the CNS from too frequent of a dosing interval in relationship to transfer half-life. 29 Unfortunately, the drug reached its peak effect in the CNS only after the patient was discharged, resulting in his death at home. Furthermore, patient 4 also demonstrates the synergistic effect of alcohol (decreasing hypoxic drive) 37,38 while the concomitant administration of the opioid produced a rightward shift in the end-expiratory CO 2 concentration.…”

Recent advances in clinical use of opioids

“…Angst et al [5] studied the pharmacokinetics and pharmacodynamics of sustained-release hydromorphone in healthy volunteers subjected to experimental pain and compared that with the results seen with the immediaterelease formulation. They found that the hydromorphone plasma concentration peaked significantly later, but was maintained significantly longer (at more than 50% of peak concentration) after sustained-release than after immediate-release hydromorphone.…”