pH, size, lipophilicity

(Smith, Roger P. A Primer of Environmental Toxicology, 1992, p. 62)

(Amdur, Mary O., John Doull, and Curtis D. Klaassen. Toxicology, 1991, p. 53)

A drug (500 mg) is administered intravenously to a 65-kg man, and plasma samples are obtained for determination of drug concentration. The concentration falls rapidly initially, as distribution occurs. First-order elimination kinetics follows. Extrapolation of this line indicates a hypothetical plasma concentration of 12 ug/ml at zero-time. The Vd is thus 500/0.012, or 41.7 l. This is indicative of distribution in total body water or drug sequestration at some nonplasma site. The half-time of drug elimination is estimated to be 3 hours.

(Goodman Gilman, Alfred, Louis S. Goodman, and Alfred Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 1980, p. 23)