Pharmacokinetics methadone

Pond SM, Kreek MJ, Tong TG, Raghunath J, Benowitz NL. Altered methadone pharmacokinetics in methadone-maintained pregnancy women. J Pharmacol Exp Ther 1985 233 1-6. 

If the nature of the time dependency is well understood and sampling is sufficient to identify model parameters, which define such expressions, a modification to the typical structural model can be explored. Specifically, as in the case of enzyme induction, changes in clearance may be expected to occur over typical time windows. By allowing the initial value of clearance, C1(0), to increase in a monoexponential manner until an asymptotic value, Cl(ss), is reached, the clearance at any time, t, can be expressed as a function of these boundary conditions and an induction rate constant, k,. Such a function (shown below) was proposed by Levy et al. and utilized by Rostami-Hodjegan et al. with certain assumptions to model methadone pharmacokinetics in opiate users. 

Zidovudine had no effect on methadone levels in one study, but there is one report of a patient requiring a modest increase in methadone dose after starting zidovudine. Similarly case reports describe patients requiring a modest increase in methadone dose after starting abacavir. Methadone can increase zidovudine serum levels, and reduce levels of abacavir, stavudine, and didano-sine from the tablet formulation, but not the enteric-coated capsule preparation. Tenofovir, and a single dose of zidovu-dine/lamivudine had no effect on methadone pharmacokinetics. 

A study in 17 subjects taking methadone found that the AUC and maximum levels of didanosine tablets were 57% and 66% lower, respectively, when compared with 10 control subjects. Trough levels of methadone did not differ from historical controls, suggesting that didanosine had no effect on methadone pharmacokinetics. A later study found that there was no reduction in the AUC of didanosine given as enteric-coated capsules. ... 

Ritonavir (dose not stated) was given to 11 healthy subjects for 14 days, with a single 5-mg dose of methadone on day 11. Ritonavir reduced the maximum serum levels of methadone by 37.8% and the AUC by 36.3%. However, in another study in 15 healthy subjects receiving methadone, ritonavir 100 mg twice daily for 7 days had no significant effect on methadone pharmacokinetics. "... 

Drug-drug interactions Cannabis Cannabis is commonly used by individuals taking methadone maintenance treatment. In a study of the effects of cannabis on methadone pharmacokinetics in 151 patients taking methadone maintenance, cannabis use and higher methadone doses were associated with a lower trough methadone concentration, believed to reflect rapid methadone clearance [122 ]. 

Kharasch ED, Hoffer C, Whittington D, Walker A, Bedynek PS. Methadone pharmacokinetics are independent of cytochrome P4503A (CYP3A) activity and gastrointestinal dmg transport insights from methadone interactions with ritonavir/indin-avir. Anesthesiology 2009 110 660-72. 

Goldstein A Brown BW (2003). Urine testing in methadone maintenance treatment applications and limitations. Journal of Substance Abuse Treatment, 25, 61-3 Gonzalez JP Brogden RN (1988). Naltrexone a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of opioid dependence. Drugs, 35, 192-213... 

Miotto K, McCann M, Basch J, Rawson R ling W (2002). Naltrexone and dysphoria fact or myth American Journal of Addictions, 11, 151-60 Mitchell TB, White JM, Somogyi AA Bodmer F (2003). Comparative pharmacodynamics and pharmacokinetics of methadone and slow-release oral morphine for maintenance treatment of opioid dependence. Drug and Alcohol Dependence, 11, 85-94 Mitchell TB, White JM, Somogyi AA Bochner F (2004). Slow-release oral morphine versus methadone a crossover comparison of patient outcomes and acceptability as maintenance pharmacotherapies for opioid dependence. Addiction, 99, 940-5 Mitka M (2003). Office-based primary care physicians called on to treat the new addict. Journal of the American Medical Association, 290, 735-6... 

GFJ has been shown to increase the exposure of carbamazepine (175), cisapride (176-179), fluvoxamine (184), losartan (188), methadone (189), scopolamine (191), and sertraline (192). However, only the interaction of GFJ with carbamazepine and cisapride seems to be clinically relevant. No alteration in exposure was observed for clozapine (180,181), heophylline (195), halo-peridol (196), and omeprazole (190). Reports of increased pharmacokinetic parameters of clozapine, theophylline, and haloperidol suggest that an interaction is unlikely to be clinically relevant. Contradicting results were reported for itraconazole (185-187), digoxin (75,183), and sildenafil (193,194). An increased effect on concomitant use of diclofenac and GFJ was observed in rats (182). Overall, the clinical relevance for this drug class appears to be low. 

Benmebarek M, Devaud C, Gex-Fabry M, et al. Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone. Clin Pharmacol Ther 2004 76(l) 55-63. 

Davis MP, Walsh D Methadone for relief of cancer pain A review of pharmacokinetics, pharmacodynamics, drug interactions and protocols of administration. Support Care Cancer 2001 9 73. [PMID 11305074]... 

Ling, Geoffrey S., Jason Gari Umans, and Charles E. Inturrisi. 1981. "Methadone Radioimmunoassay and Pharmacokinetics in the Rat." Journal of Pharmacology and Experimental Therapeutics 217 147-51. 

Berkowitz, B.A. The relationship of pharmacokinetics to pharmacological activity morphine, methadone and naloxone, Clin. Pharmacokinet. 1976, 1, 219-230. 

Olsen, G.D., Wendel, H.A., Livermore, J.D., Leger, R.M., Lynn, R.K., Gerber, N. Clinical effects and pharmacokinetics of racemic methadone and its optical isomers, Clin. Pharmacol. Ther. 1977, 21, 147-157. 

Members of the group of natural, semisynthetic, or synthetic alkaloid compounds prepared from opium are referred to as opioids. This group includes natural compounds usually denoted opiates, such as morphine and codeine, and the synthetic and semi synthetic compounds such as oxycodone, buprenorphine, fentanyl, methadone, and tramadol. The pharmacological effects and pharmacokinetic parameters of these drugs share many common characteristics and are illustrated with the prototypic drug in this class, morphine. 

In addition to knowledge about the clinical efficacy, adverse effect profile, and likelihood of emergence of resistance, the physician caring for an HIV-infected patient must be well versed in basic pharmacokinetics as well. Such patients are frequently taking multiple medications, including combinations of antiretroviral agents, prophylaxis or treatment for opportunistic infections, and opioid pain medications or methadone for maintenance therapy. 

Trapnell CB, Klecker RW, Jamis-Dow C, et al. Glucuronidation of 3 -azido-3 -deoxythymidine (ZDV) by human liver microsomes relevance to clinical pharmacokinetic interactions with atovaquone, fluconazole, methadone, and valproic acid. Antimicrob Agents Chemother 1998 42(7) 1592-1596. 

Pharmacokinetics Readily absorbed following oral administration, methadone has a longer duration of action than does morphine. It accumulates in tissues, where it remains bound to protein from which it is slowly released. The drug is biotransformed in the liver and excreted in the urine, mainly as inactive metabolites. 

Clarke SM, Mulcahy FM, Tjia J, Reynolds HE, Gibbons SE, Barry MG, Back DJ. The pharmacokinetics of methadone in HIV-positive patients receiving the non-nucleoside reverse transcriptase inhibitor efavirenz. Br J Clin Pharmacol 2001 51(3) 213-7. 

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