[Determinants of serum pentamidine concentration in the human]

By means of serial measurements of pentamidine in plasma, urine and feces the significance of biologically available dose, volume of distribution, elimination and dose interval for serum concentration is investigated in patients with AIDS and bone marrow transplantation after inhaled and intravenous application. Aerosolisation of the drug yields to serum concentration mostly below the detection limit (HPLC). In urine only 0.15 to 0.8% of the substance biologically available in the lung are measured as unaltered pentamidine-base. After i.v. infusion the dose dependent low serum concentrations of 30 to 100 ng/ml indicate a fast distribution in peripheral compartments from which a very slow deliberation is seen. The half-life of the drug is also dose dependent and amounts under clinical conditions at minimum four days. The fecal excretion is found to be only one third of that measured in urine. A difference in the kinetic of elimination between bone marrow transplantated and AIDS-patients could not be evaluated. For clinical therapy the most important pharmacokinetic variable seems to be the terminal elimination constant which would implicate a prolongation of the common dose interval.