Christopher William Hand

Oral morphine in cancer pain: influences on morphine and metabolite concentration

One hundred fifty‐one patients with chronic cancer pain were studied during chronic treatment with oral morphine. Plasma concentrations of morphine and metabolites (M3G and M6G) were measured. The ratio of plasma morphine to metabolites was not affected by dose. Generalized linear interactive modeling analysis using morphine dose, age, sex, renal and hepatic dysfunction, and concomitant medication as explanatory variables accounted for 70% of the variance in plasma concentrations of morphine, morphine‐3‐glucuronide (M3G) and morphine‐6‐glucuronide (M6G). Increasing morphine dose was a significant factor for increased plasma concentrations of morphine, M3G, and M6G. Other significant factors were: age greater than 70 years (increased M3G and M6G plasma concentrations), plasma creatinine >150 µmol/L (increased M3G and M6G plasma concentrations), male sex (decreased morphine and M6G plasma concentrations), raised creatinine plus coadministration of tricyclic antidepressants (increased M3G plasma concentrations), ranitidine (increased morphine plasma concentrations), and raised creatinine plus coadministration of ranitidine (increased M6G plasma concentrations).

Comparison of GC-MS and EIA Results for the Analysis of Methadone in Oral Fluid

The purpose of these studies was to evaluate the performance characteristics of the Cozart Microplate Enzyme Immunoassay (EIA) for the determination of methadone in oral fluid from patients in a drug misuse treatment program. Oral fluid specimens were collected using the Cozart RapiScan Collection system from 198 donors who were receiving treatment for their addiction and were monitored for drug misuse. Oral fluid specimens were also collected from forty volunteer donors who were not drug users. The specimens were analyzed in the laboratory by EIA and then analysed for methadone and its main metabolite EDDP by gas chromatography-mass spectrometry (GC-MS). A total of 103 samples were confirmed positive for methadone. The Cozart Microplate EIA for d-Methadone in oral fluid using a cutoff of 30 ng/mL in diluted oral fluid had a sensitivity of 91.3% +/- 2.8% and a specificity of 100% +/- 1.0% vs. GC-MS.

Epinephrine reduces systemic absorption of extradural diacetylmorphine.

The effect of epinephrine on the vascular absorption of morphine from the extradural space is uncertain; this study examined the effect of epinephrine on the related but more lipophilic opiate diacetylmorphine (diamorphine, heroin) because any effects of vasoconstriction on diacetylmorphine absorption should be maximally apparent. With this experiment, we hoped to resolve whether epinephrine does or does not alter vascular absorption of extradurally injected opiates. Thirty patients undergoing lumbar laminectomy were given either extradural diacetylmorphine, 5 mg, extradural diacetylmorphine, 5 mg with 1:200,000 epinephrine, or 1:200,000 epinephrine followed 5 min later by 5 mg extradural diacetylmorphine. Plasma morphine concentrations were measured by radioimmunoassay because of the rapid conversion of diacetylmorphine to morphine in plasma; repeated blood samples were obtained the first 30 min after injection into the epidural space. Significantly lower plasma morphine levels occurred between 3 and 20 min when epinephrine was added to diacetylmorphine. Peak plasma morphine levels (mean ± SEM) were 179 ± 37 nmol/L with diacetylmorphine alone, 87 ± 16 nmol/L with diacetylmorphine and epinephrine given together and 44 ± 11 nmoll L with epinephrine pretreatment, all significantly different from one another. The mean peak plasma morphine concentration was 8.7 ± 1.1 min for diacetylmorphine alone, but addition of epinephrine (together or sequentially) meant that 15 of 20 patients had no peak level before 120 min. Epinephrine reduced absorption of diacetylmorphine from the extradural site by at least 55% over the first 30 min. The incidence of patients with more than 9 hr analgesic duration was significantly (P = 0.033) greater in patients who had diacetylmorphine and epinephrine. The use of diacetylmorphine as a model for lipophilic opiates showed that addition of epinephrine not only reduced systemic absorption but also increased analgesic duration. The addition of epinephrine to similarly lipophilic opiates should have the same clinically desirable consequence.

Sensitivity and Specificity of the Cozart Microplate EIA Cocaine Oral Fluid at Proposed Screening and Confirmation Cutoffs

BACKGROUND Oral fluid is currently being evaluated as an alternative matrix for monitoring illicit drugs in federally mandated workplace drug testing, for addiction treatment programs, and for driving under the influence testing. The sensitivity, specificity, and efficiency of the Cozart Microplate EIA Cocaine Oral Fluid Kit (COC ELISA) were determined by comparison with gas chromatography-mass spectrometry (GC/MS) results at screening and confirmation cutoffs proposed in the US and UK. METHOD Oral fluid was collected by expectoration after citric acid candy stimulation or with Salivette neutral cotton swabs or Salivette citric acid-treated cotton swabs before and after cocaine (COC) administration. Specimens (n = 1468) were analyzed with the COC ELISA for screening and with solid-phase extraction followed by GC/MS for confirmation. Three screening cutoffs (10, 20, and 30 microg/L) and four GC/MS cutoffs (2.5, 8, 10, and 15 microg/L COC, benzoylecgonine, and/or ecgonine methyl ester) were evaluated. GC/MS limit of quantification was 2.5 micro g/L for all analytes. RESULTS COC ELISA interassay imprecision (CV; n = 19) was 16% at 16.7 microg/L and 12% at 81.8 microg/L. With the 2.5, 8, 10, and 15 microg/L GC/MS cutoffs, 59.0%, 54.7%, 52.7%, and 48.7% of the oral fluid specimens were positive, respectively. Sensitivity, specificity, and efficiency were 92.2%, 84.7%, and 88.8%, respectively, for the suggested Substance Abuse and Mental Health Services Administration (SAMHSA) cutoffs and 90.2%, 89.2%, and 89.7% for cutoffs currently used in the UK. CONCLUSIONS COC ELISA had suitable sensitivity, specificity, and efficiency for identifying COC exposure at both the proposed SAMHSA and UK cutoffs. Sensitivity, specificity, and efficiency were >84% for both cutoffs, but 92 additional true-positive samples were identified with the SAMHSA cutoffs.

Morphine Kinetics and Kidney Transplantation: Morphine Removal is Influenced by Renal Ischemia

Morphine plasma concentrations were determined in six patients receiving kidney transplants from living-related donors, and nine patients receiving kidney transplants from cadavers. The total cold ischemic time was about 2 hr for kidneys from living-related donors and 14 hr for those from cadavers. After an intravenous bolus dose of morphine, plasma morphine concentrations decreased to a plateau that lasted for several hours; morphine elimination resumed when the transplanted kidney began to clear creatinine. The duration of the total cold ischemic time was significantly related to both the duration of the plateau in morphine concentration (P = 0.008) and the first postoperative day creatinine clearance (P = 0.021). Morphine elimination half-life after the plateau was related to first postoperative day creatinine clearance (P < 0.001). It was concluded that morphine elimination depended upon intact renal function.

Analysis of Drugs in Saliva

Investigation of the involvement of drugs in impaired driving would be facilitated by a roadside test for drugs in saliva such as currently exists for alcohol in breath. Collection of saliva is simple and noninvasive. It can be carried out by the suspect while under observation. The feasibility of detecting drugs in saliva samples obtained from impaired drivers was first investigated by Peel et al. (1). They found that the presence of drugs in saliva correlated well with officer judgements of driving while intoxicated.