Abstract
Peg-interferon-alpha-2a (PEG-IFN) has been used all over the world including Japan as the standard of care for chronic hepatitis C (CHC). PEG-IFN causes platelet count decrease, while CHC patients with compensated liver cirrhosis has low baseline of platelet. To use PEG-IFN more safely in the patients, we analyzed longitudinal platelet profile affected by PEG-IFN with a pharmacokinetic-pharmacodynamic model. Platelet count and serum PEG-IFN concentration obtained from Japanese clinical study on 40 patients were analyzed. Serum PEG-IFN concentration profile was fitted with an open 1-compartment model and the platelet profile was fitted with a turnover model. After the final model was fixed, the platelet profiles were simulated with various platelet baselines. The simulation revealed that according to PEG-IFN administration platelets decreased gradually and reached steady state within 12 weeks, and almost subjects would not have lower platelet count than the criteria for discontinuation of the treatment. Once administration was discontinued, platelets recovered up to the baseline within several weeks. In conclusion, platelet count was predicted to be about 30% (5th-95th percentiles in 1000 simulation: 11%-66%) decrease and to return to baseline value in 4 to 8 weeks after the last administration of PEG-IFN.
