Yazarlar : Müller C, Murawski N, Wiesen MH, et al

Yayın : Blood.

Yayın Yılı : 2012

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22337718

Konu : Lenfoma

Literatür İçeriği :

Abstract

Because of limited data available, pharmacokinetics of 8 doses rituximab (375 mg/m(2)) given in combination with CHOP-14 was investigated in 20 elderly patients with DLBCL. Blood samples were obtained 10 minutes before and after each rituximab infusion, and 1 week, and 1, 2, 3, 6 and 9 months after the last infusion. Rituximab serum levels were determined by ELISA. Population pharmacokinetic modeling was performed with nonlinear mixed effect modeling software (NONMEM VI). Serum concentration-time data were fitted into an open two-compartment model and total clearance (Cl), central compartment volume (V(c)), intercompartment clearance (Q) and volume of distribution at steady-state (Vd(ss)) were investigated. Cl was 9.43 ml/h and Vd(ss) 9.61 l. Rituximab clearance was significantly reduced (8.21 ml/h vs. 12.68 ml/h; p=0.003) and elimination half life was significantly prolonged in women compared to men (t(1/2β)=30.7 vs. t(1/2β)=24.7 d; p=0.003). Body weight also impacted on volume of distribution (0.1 l increase of Vd(ss) per kilogram of body weight above median weight of 75 kg). Thus, a gender-dependent effect and the higher weight of males contribute to their faster rituximab clearance, which might explain why elderly male patients with DLBCL benefit less from the addition of rituximab to CHOP than females. The trials were registered on www.clinicaltrials.gov, number NCT00052936 and as EU-20243 (RICOVER-60 Trial) and as EU-20534 and NCT00726700 (Pegfilgrastim Trial)

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