ThioTEPA pharmacokinetics during intravesical chemotherapy and the influence of Tween 80.
A pharmacokinetic study of randomised crossover design was carried out in which eight patients with recurrent stage pTa or pT1 transitional cell carcinoma of the bladder were given thioTEPA (30 mg) in distilled water or in 10% (v/v) Tween 80 (30 ml) intravesically for 2 h, followed 3 months later by the alternative treatment. ThioTEPA and its primary metabolite, TEPA, were measured in plasma and urine using a sensitive and specific chromatographic assay. Large differences between patients were observed in the proportion of thioTEPA absorbed, ranging from 20%-78%. Peak plasma levels of thioTEPA were observed within 1 h of intravesical administration. By 2 h after administration the plasma levels of TEPA were similar to those of thioTEPA and, in contrast to those of the parent compound, remained at a similar level over the next 4 h. The rate of absorption of thioTEPA was not influenced by Tween 80, but it did cause statistically significant increases in mean peak plasma levels (from 101 to 154 ng/ml) and mean AUC values (from 0.376 to 0.496 micrograms h per ml) and a decrease in the mean half-life (from 1.83 to 1.25 h). To obtain plasma levels similar to those achieved after instillation with thioTEPA alone, the dose should be reduced with Tween 80.
University College London, Institute of Urology, St Pauls Hospital, London, UK.
J R
JR
Masters
B J
BJ
McDermott
W E
WE
Jenkins
E
E
Fenwick
P J
PJ
Shah
A R
AR
Mundy
P M
PM
Loadman
M C
MC
Bibby
D000042:Absorption; D000283:Administration, Intravesical; D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011136:Polysorbates / Q000494:pharmacology*; D011897:Random Allocation; D013852:Thiotepa / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013721:Triethylenephosphoramide / Q000493:pharmacokinetics; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D011136:Polysorbates; D013852:Thiotepa; D013721:Triethylenephosphoramide