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Fluoride (3 mg) was administered as a continous intravenous infusion during 30 min to 6 healthy subjects. Plasma concentrations and urinary excretion of fluoride in these experiments were compared with those obtained following oral administration of 2.82 mg, 4.50 mg, 5.64 mg, and 9.40 mg in the form of tablets and capsules. There were large day-to-day variations in the renal clearance of fluoride. This was shown to be due to differences in the urinary flow, an increase in flow causing an increase in renal clearance. The mean value of renal clearance from all experiments was 66.2 +/- 27.8 (SD; n = 16) ml/min. The extrarenal clearance, suggested to represent mainly the clearance to the bone pool, showed less interindividual variation: mean 110.3 +/- 32.3 (SD; n = 6) ml/min; the fraction remaining in the bone pool was highly consistent: 0.579 +/- 0.049 (SD; n = 6). When apparrent bioavailability was calculated from plasma and from urinary data, there was a great intra- and intersubject variation, as well as poor agreement between the two methods of calculations. This was found to be due to the day-to-day variation in renal clearance, which, in turn, varied with urinary flow. By use of equations that corrected for these variations, it was found that the bioavailability of sodium fluoride tablets is approximately 100%.

We report here a simple method involving urine creatine measurements for testing authenticity and reducing false-negative results in urine testing for drugs of abuse. Urinary creatinine in consecutive patient samples (n = 176) ranged between 0.1 and 31.9 mmol/L (mean 9.8 +/- SD 6.2) and the osmolality in these urines ranged between 49 and 1183 mOsm/kg (mean 595 +/- SD 276). With other consecutive samples in which creatinine was (arbitrarily chosen) less than 4.3 mmol/L (n = 85), the correlation with osmolality was lower. In 10 randomly selected urine samples from different patients, all "clean" for all drugs of abuse in initial immunological drug testing with approved methodology (in which creatinine was less than 4.3 mmol/L and osmolality was less than 200 mOsm/kg), five patients turned out to be drug positive after a simple concentration by volume. In a formerly heavy smoker of cannabis, the excretion of cannabinoids and creatinine was monitored for 93 days. The substances showed very good correlation throughout this period (r = 0.93, P less than 0.001), whereas simple measurements of cannabinoid concentrations would have falsely indicated several relapses of cannabis abuse. Urine samples used in drug-abuse testing should be tested for creatinine; if creatinine is less than 4.0 mmol/L, negative results for drugs may not be valid.

The doses of fluoride (F) recommended in the literature for caries prevention and for the treatment of osteoporosis vary. This partly reflects inadequate knowledge of F pharmacokinetics. In the present study various single and multiple oral doses of F were given to eight volunteers, who had a strictly controlled F intake in the diet. The resulting plasma and parotid saliva concentrations as well as urinary output of F were measured. The plasma data fitted a two-compartment open model with a beta-slope half-life ranging between 2 and 9 h. Plasma clearance was 0.15+/-0.02 (SD) liter/kg/h. Data from the highest dose (10 mg) were fitted to both two- and three-compartment models, and there was no significant difference between them. Multiple doses of F 3.0 Or 4.5 mg yielded steady state concentrations ranging from 54 to 145 ng/ml. About 50 per cent of the given dose was recovered in the urine, which is indicative of considerable accumulation in the body. The saliva F/plasma F concentration ratio was 0.64 with a coefficient of variation of 5%.

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Plasma concentrations of codeine and its demethylated metabolite, morphine, were determined after single and repeated oral administration of codeine. Twelve healthy volunteers received two doses of codeine 60 mg, 2.8 h apart. In order to achieve steady-state conditions codeine 60 mg was then taken every 8 h for a further five doses. The plasma concentrations of codeine and morphine after the first, second and seventh doses were analyzed by GC-MS. The maximum plasma concentrations of codeine and morphine were reached about 1 h after administration and this time interval did not change on repeated administration. The peak plasma codeine was higher after the second dose of codeine than after the first and the concentration resembled that at steady-state. For morphine, the plasma concentration did not increase significantly after the second dose. Both after a single dose and during steady-state the plasma concentration of morphine was only 2-3% of that of codeine. It seems unlikely that morphine plays a significant role in the analgesic efficacy of single or repeated doses of codeine.

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