Kinetic parameters of metformin (N,N-dimethylbiguanide), an anti-diabetic reported to be associated with a lower number of episodes of lactic acidosis than phenformin, were determined in volunteers with normal renal function and in patients with different degrees of renal impairment. Drug in body fluids was measured by a highly specific and sensitive mass fragmentographic method, after the formation of a triazine derivative, obtained with heptafluorobutyric anhydride. The half-life (t 1/2) for the elimination of drug from plasma after intravenous injection in 5 normal subjects (1.52 +/- 0.3 hr) (mean +/- SD) was shorter than that reported for phenformin by a similar assay method (7 to 15 hr). The mean t 1/2 in 5 renal patients was 4.94 +/- 1.11 hr, and a correlation was observed between t 1/2 of drug from plasma and creatinine clearance. After oral administration of metformin tablets, drug recovery in urines was only 37.6%, possibly not as a consequence of low bioavailability (a similar low recovery was found after oral administration of the metformin solution used for the intravenous studies), but of binding to the intestinal wall, as shown in animal and clinical studies with metformin and other biguanides. Metformin is rapidly eliminated through active secretion by the kidney (mean renal clearance, 440.8 ml/min)--it is neither metabolized nor protein bound in plasma. The very brief plasma t 1/2 makes significant cumulation, with a standard tid regimen, unlikely. These findings may help explain the lower incidence of toxic effects, particularly lactic acidosis, than after phenformin.

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Earth-and space-based observations provide synergistic information for space mission encounters by providing data over longer timescales, at different wavelengths and using techniques that are impossible with an in situ flyby. We report here such observations in support of the EPOXI spacecraft flyby of comet 103P/Hartley 2. The nucleus is small and dark, and exhibited a very rapidly changing rotation period. Prior to the onset of activity, the period

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