Integrated Model to Describe Morphine Pharmacokinetics in Humans

Abstract

The pharmacokinetics (PK) of morphine has been extensively investigated. Though different publications have focused on the various aspects of morphine PK, none have quantitatively interpreted morphine PK across different publications. The objective of this research is to summarize the current understanding of morphine PK in humans quantitatively. In this research, a parent-metabolite compartmental PK modeling approach was used to summarize the current understanding of morphine PK in humans. Plasma concentration-time profiles and cumulative urine recovery time profiles of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were digitized from the previous publications to develop the parent-metabolite PK model. The parent-metabolite PK model successfully described the plasma concentration-time profiles and cumulative urine recovery of morphine as well as its two major metabolites, morphine-3-glucuronide and morphine-6-glucuronide, after intravenous and oral administration of morphine. This research separated out the first-pass effect on morphine metabolism after oral administration. By integrating these results with two mass balance studies of morphine, a clear picture of morphine absorption and disposition is given. Though the results are mainly based on data collected from healthy volunteers or patients whose disease is not expected to impact morphine PK, the parent-metabolite model sets a framework to further evaluate morphine PK in special populations, such as pediatrics and patients with renal impairment.

Pharmacometric approach to assist dosage regimen design in neonates undergoing therapeutic hypothermia

“…The meta-modeling method was reported to help in the identification of a generalizable model that can be used to provide dosing recommendations in a variety of populations. 18,19 Reduced CL during TH has been reported for amikacin, amoxicillin, and ampicillin. [20][21][22] Seven reports on gentamicin during PATH were used in the meta-modeling procedure of the present study.…”

Assessment in vitro of interactions between anti-cancer drugs and noncancer drugs commonly used by cancer patients

“…Although loperamide based on these findings has been suggested to be a potential anticancer drug, its low bioavailability resulting in plasma concentration considerably lower than those inhibiting cell proliferation and inducing apoptosis seemingly preclude such use of loperamide. Morphine, extensively used to treat cancer pain, on the other hand, may reach plasma concentrations more closely to those showing tumor cell proliferation inhibition in vitro [ 28 ]. However, to our knowledge, there is no report on tumor remission induced by morphine in cancer patients.…”

Medication considerations including safety and its principles in geriatric dentistry

“…Apart from reducing the first-pass effect of drugs, aging also increases their bioavailability and blood concentrations. Accordingly, when used in older adults, the dose of some drugs, such as propranolol and morphine, needs to be adjusted [13]. In older adults, kidney mass and nephrons decrease, and the average glomerular filtration rate (GFR) and renal blood flow decrease [14].…”