Pharmacokinetics of intravenous ATP in cancer patients

Objective: To characterise the pharmacokinetics of adenosine 5'-triphosphate (ATP) in patients with lung cancer after i.v. administration of different ATP dosages. Methods: Twenty-eight patients received a total of 176 i.v. ATP courses of 30 h. Fifty-two infusions were given as low-dose infusions of 25-40 mu g kg(-1) min(-1), 47 as middle-dose infusions of 45-60 mu g kg(-1) min(-1) and 77 as high-dose infusions of 65-75 mu g kg(-1) min(-1) ATP. Kinetic data of ATP concentrations in erythrocytes were available from 124 ATP courses. Results are expressed as mean +/- SEM. Results: Most ATP courses in cancer patients were without side effects (64%), and side effects occurring in the remaining courses were mild and transient, resolving within minutes after decreasing the infusion rate. Baseline ATP concentration in erythrocytes was 1554 +/- 51 mu mol l(-1) ATP plateau levels at 24 h were significantly increased by 53 +/- 3, 56 +/- 3 and 69 +/- 2% after low-dose, middle-dose and high-dose ATP infusions, respectively. At the same time, significant increases in plasma uric acid concentrations were observed: 0.06 +/- 0.01, 0.11 +/- 0.01 and 0.16 +/- 0.01 mmol l(-1), respectively. The mean half-time for disappearance of ATP from erythrocytes, measured in five patients, was 5.9 +/- 0.5 h. Conclusions: During constant i.v. infusion of ATP in lung cancer patients, ATP is taken up by erythrocytes and reaches dose-dependent plateau levels 50-70% above basal concentrations at approximately 24 h.