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Titolo:
Steady-state pharmacokinetics and pharmacodynamics in methadone maintenance patients: Comparison of those who do and do not experience withdrawal andconcentration-effect relationships
Autore:
Dyer, KR; Foster, DJR; White, JM; Somogyi, AA; Menelaou, A; Bochner, F;
Indirizzi:
Univ Adelaide, Dept Expt & Clin Pharmacol, Adelaide, SA 5005, Australia Univ Adelaide Adelaide SA Australia 5005 ol, Adelaide, SA 5005, Australia Univ Adelaide, Dept Psychol, Adelaide, SA 5005, Australia Univ Adelaide Adelaide SA Australia 5005 ol, Adelaide, SA 5005, Australia Royal Adelaide Hosp, Dept Clin Pharmacol, Adelaide, SA 5000, Australia Royal Adelaide Hosp Adelaide SA Australia 5000 elaide, SA 5000, Australia
Titolo Testata:
CLINICAL PHARMACOLOGY & THERAPEUTICS
fascicolo: 6, volume: 65, anno: 1999,
pagine: 685 - 694
SICI:
0009-9236(199906)65:6<685:SPAPIM>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
SERUM METHADONE; CANCER PAIN; ADDICTS; DISPOSITION; DEPENDENCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Bochner, F Univ Adelaide, Dept Expt & Clin Pharmacol, Adelaide, SA 5005, Australia Univ Adelaide Adelaide SA Australia 5005 e, SA 5005, Australia
Citazione:
K.R. Dyer et al., "Steady-state pharmacokinetics and pharmacodynamics in methadone maintenance patients: Comparison of those who do and do not experience withdrawal andconcentration-effect relationships", CLIN PHARM, 65(6), 1999, pp. 685-694

Abstract

Objective: To determine plasma racemic methadone concentration-effect relationships for subjective and objective responses and whether pharmacokinetic and/or pharmacodynamic factors influence withdrawal severity. Methods: Eighteen patients enrolled in a public methadone maintenance program, nine of whom experienced significant withdrawal, received constant doses of methadone once daily for at least 2 months. During an interdosing interval, 13 blood samples were collected to measure plasma racemic methadone concentrations (patients); subjective (withdrawal severity, direct opioid effects, and pain threshold) and objective (pupil diameter and respiratory rate) opioid effects were quantified on 11 occasions (all participants). Thesigmoid E-max model was used to relate plasma concentrations and effects and to calculate the slope factor (N). The rate of decline in plasma concentration during each hour from the peak to the trough concentration was calculated. Results: There was an inverse relationship between plasma concentrations and withdrawal severity and pupil diameter, as well as a direct relationshipwith subjective opioid effects and pain threshold. The mean N values were 5.4 +/- 0.9 for withdrawal severity, 5.1 +/- 1.1 for subjective opioid effects, 1.2 +/- 0.1 for pupil diameter, and 2.8 +/- 0.7 for pain threshold. Withdrawal severity correlated with the maximum rate of decrease in plasma concentration (P < .01). There were no differences between those who reportedsignificant withdrawal and those who did not with respect to mean area under the plasma concentration versus time curve and predose plasma concentration, but maximal rate of decline was greater in the former group (74.5 versus 42.1 ng/mL/h). Conclusions:In this group of long-term methadone-maintained recipients, opioid responses were strongly correlated with changes in plasma racemic methadone concentrations. For the subjective responses, notably withdrawal, small changes in plasma concentrations translate into relatively large changesin effect; therefore, clinically important withdrawal is a consequence of more rapid decline in methadone concentration.

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Documento generato il 04/04/20 alle ore 08:16:41