(67) ,ug m1-1, respectively, at the highest dose. Median tmax in plasma was 6.5 h and in erythrocytes 24.5 h, when approximately 60% of the administered dose was in the target tissue. Plasma drug concentrations fell biexponentially with commencement of the apparent terminal elimination phase at approximately 24 h. The terminal elimination half-life from plasma increased with dose (r = 0.77; P < 0.0001) from 133-190 h at 400 mg to a mean (s.d.) of 289 (30) h at 3600 mg. Erythrocyte drug concentrations declined monoexponentially with a half-life that was always shorter than the apparent terminal halflife in plasma: overall mean (95% CI) of t1/2 erythrocyte/t1/2 plasma ratio was 0.57 (0.53, 0.61). The erythrocyte AUC/plasma AUC ratio increased with dose (r = 0.67; P < 0.001). 4 The proportion of haemoglobin modified to a form with high oxygen affinity (% MOD) increased in a dose-related manner above doses of 800 mg reaching 19-26% after the 3600 mg dose. The % MOD was directly proportional to erythrocyte drug concentrations and declined in parallel during the elimination phase. 5 The drug was well tolerated, with no clear effects on resting or exercise heart rates or blood pressures. Small increases in reticulocyte counts were seen following doses of 2800 and 3600 mg suggesting stimulation of erythropoiesis.

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A prospective multi-agency survey of problem drug use associated with illicit drugs and solvents in the city of Bristol in 1984-1985 found 759 problem drug users, giving a period prevalence rate of 0.4-0.8% of those aged 10-44 years. The group was a young one, with 92% under the age of 35. Over half had problems associated with opiates, mainly illicit heroin; 17% had problems associated with solvents, 9% with cannabis, 13% with stimulants, mainly illicit amphetamine, and 3% with hallucinogens. There was little indication of problematic use of barbiturates or cocaine. The problems associated with drugs and solvents were wide-ranging and not specific for individual drugs. Future community surveys would find it cost-effective to concentrate on the five best sources identified here, and to supplement these with indications of drug-taking among teenagers. The difficulties of using the definition of problem drug use for research and the value of case-register surveys for community drug monitoring are discussed.

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