PKP-001 Influence of gender and body size on 5-fluorouracil pharmacokinetic. (14th February 2016)

• Record Type: Journal Article
• Authors: Egüés, A; Aldaz, A; Alzueta, N; Rodriguez, J
• Is Part Of: European journal of hospital pharmacy. Volume 23(2016)Supplement 1
• Page Start: A178
• Page End: A178
• Publication Date: 2016-02-14
• Subjects: Pharmacy -- Periodicals; Hospital pharmacies -- Periodicals; 615.1
• DOI: 10.1136/ejhpharm-2016-000875.404
• Languages: English
• ISSNs: 2047-9956

Abstract

Abstract : Background: Conventional body surface area based dosing of 5-fluorouracil (5-FU) is associated with significant inter- and intra-individual variability in plasma levels of 5-FU. Several potential sources of pharmacokinetic variation have been proposed, including pharmacogenetic differences, organ function, disease state, circadian rhythm and drug specific factors, such as schedule of administration and interactions with other drugs and herbal medicines. Purpose: To evaluate the influence of gender and body size on 5-FU pharmacokinetics. Material and methods: We studied adult patients with gastrointestinal cancer receiving 5-FU based therapy. A total of 386 chemotherapy cycles were analysed. Plasma concentrations of 5-FU were obtained and pharmacokinetic parameters were estimated by Bayesian methodology fitted to a one compartment model for individual 5-FU dose adjustment. Demographic characteristics of the patients were collected and their relationship with 5-FU pharmacokinetics evaluated. Results: 184 patients with a mean±SD age of 62 ± 10.8 years (range 36–85) were included. Mean±SD weight was 72.43 ± 14.47 kg. 28 patients (15%) were obese and 9 (4.9%) were underweight. Tumour locations were colorectal in 91 cases, pancreatic in 40 and gastric in 35. The mean value for 5-FU clearance (CL) was 179.28 L/h with a low interindividual variability of 28.6% owing to pharmacokinetic monitoring and an elimination half life (T1/2 ) of 7.83 min. In a multivariate regression analysis, we showed a significant positive association between gender, body size and 5-FU CL. Women compared with men had lower 5-FU CL (157 vs 189 L/h, p < 0.01). Obese patients has a higher CL and distribution volume (Vd): 197.3 L/h and 38.6 L, respectively, vs 177.3 L/h and 31.9 L in leaner patients. In contrast, we identified a subgroup (n = 21) of patients with SC <1.6 and < 55Kg, in which 5-FU exposure was significantly higher due to the lower 5-FU CL (146 vs 183 L/h) and higher T1/2 (8.03 vs 7.1min). 76.2% of this subgroup were women. Conclusion: 5-FU pharmacokinetics were notably influenced by body size and gender. There was a subgroup of patients, with especially low body size, in which 5-FU elimination was reduced. No conflict of interest.