Role of CYP3A5 in abnormal clearance of methadone.
OBJECTIVE
To report a case of unusually low concentrations of methadone in a polydrug abuser during maintenance treatment with methadone.


METHODS
A 25-year-old man (weight 55 kg, height 165 cm) with a 12-year history of polydrug abuse was admitted to an opiates withdrawal methadone program. At the time of our observation, he was using both cannabinoids and heroin; no other medical conditions were discovered. Within the opiates withdrawal methadone program, under medical supervision, the patient started methadone therapy (20 mg/day). Two weeks later, an Abuscreen assay for methadone screening in the urine was negative and, to prevent the development of withdrawal symptoms, the dose of methadone was increased to 60 mg/day. One day later, the patient was asked to collect another urine sample in the presence of a nurse. The Abuscreen for methadone in urine remained negative. Evaluation of urinary samples collected over 24 hours documented low concentrations of methadone and high levels of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (the primary metabolite of methadone). Evaluation for the presence of the most common polymorphisms in the cytochrome P450 and P-glycoprotein genes showed that the patient was heterozygous for the CYP3A5(*)1 allele and for 2 single nucleotide polymorphisms in the P-glycoprotein gene (1236C/T and 3435C/T).


CONCLUSIONS
In this patient, poor methadone adherence was ruled out because of the presence of physicians and nurses during both methadone maintenance treatment and Abuscreen screening. Moreover, because the patient reported only heroin and cannabis at the time of evaluation, drug interactions were ruled out as possible causes for the rapid clearance of methadone.


CONCLUSIONS
In this case, CYP3A5 polymorphism may have played a role in the rapid methadone metabolism.
De Fazio
Salvatore
S
Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, University Magna Graecia of Catanzaro, Mater Domini University Hospital, Catanzaro, Italy.
Gallelli
Luca
L
De Siena
Antonella
A
De Sarro
Giovambattista
G
Scordo
Maria Gabriella
MG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000483:Alleles; D000701:Analgesics, Opioid / Q000378:metabolism* / Q000652:urine; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008691:Methadone / Q000378:metabolism* / Q000652:urine; D020641:Polymorphism, Single Nucleotide; D011759:Pyrrolidines / Q000652:urine; D015813:Substance Abuse Detection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000701:Analgesics, Opioid; D011759:Pyrrolidines; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D008691:Methadone; C010724:2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine