Influence of mesna on the pharmacokinetics of cisplatin and carboplatin in pediatric cancer patients.
Mesna, a reactive thiol, often encounters cisplatin and carboplatin in combination protocols involving oxazaphosphorines and platinum drugs. This co-administration might be unfavorable based on the inactivation of platinum drugs by thiol groups in vitro. We investigated whether mesna influences the pharmacokinetics of platinum drugs when co-administered with cisplatin or carboplatin. The pharmacokinetics of platinum drugs were investigated in 18 pediatric patients receiving either cisplatin or carboplatin in a combination with or without mesna. In cisplatin patients, a decrease in the distribution clearance of total platinum was observed when mesna was co-administered (CLd, 2.2 +/- 0.1 mL/min.kg; n = 3), compared to cisplatin without mesna (CLd, 4.8 +/- 1.5 mL/min.kg; n = 5) (p = 0.029, t-test). This might have been caused by an influence of mesna in slowing down the protein binding of cisplatin since a trend (p = 0.057) in prolonged distribution half-life of total platinum was also observed when mesna was present (t(1/2a) 65 +/- 21 min; n = 3) compared to cisplatin without mesna (t(1/2a), 32 +/- 18 min; n = 5). However, the impact of these changes on the area under the concentration time curve (AUC), total clearance (CLt), and volume of distribution (V) for total platinum and ultrafilterable platinum species was hardly noticeable. In carboplatin patients, when mesna was co-administered: AUC (2.5 +/- 0.4 mg.min/mL.400 mg/m2; n = 5) CLt, (6.8 +/- 5.1 mL/min.kg; n = 6), and V (0.7 +/- 0.4 L/kg; n = 6) for ultrafilterable platinum species were not significantly different from when carboplatin were administered without mesna: AUC (2.3 +/- 1.3 mg.min/mL.400 mg/m2; n = 4), CLt (5.8 +/- 4.6 mL/min.kg; n = 5), and V (1.1 +/- 1.1 L/kg; n = 5). Hence, mesna does not significantly influence the pharmacokinetics of cisplatin and carboplatin in pediatric cancer patients.
Kangarloo
Shahbal B
SB
Department of Oncology, Faculty of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331 29th Street NW, Calgary, Alberta T2N 4N2 Canada.
Gangopadhyay
Suman B
SB
Syme
Rachel M
RM
Wolff
Johannes E A
JE
Glück
Stefan
S
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015080:Mesna / Q000008:administration & dosage; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage; D013997:Time Factors
D000970:Antineoplastic Agents; D020011:Protective Agents; D016190:Carboplatin; D015080:Mesna; D002945:Cisplatin