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Pharmacokinetics of intravenous ATP in cancer patients
H J Agteresch1, P C Dagnelie, T Rietveld
1Department of Internal Medicine, Erasmus University Medical Centre Rotterdam, The Netherlands.
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 microg kg(-1) min(-1), 47 as middle-dose infusions of 45-60 microg kg(-1) min(-1) and 77 as high-dose infusions of 65-75 microg 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 1,554 +/- 51 micromol 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.