Pharmacokinetics of rhGH decorated by polyethylene glycol in rat in vivo / 药学学报

To study the pharmacokinetics of rhGH decorated by polyethylene glycol (PEG-rhGH) after sc administration in rat, serum PEG-rhGH concentrations were measured by 125I labeled method after sc in rat, the pharmacokinetic model and parameters were fitted and calculated by the 3P97 program. After sc injection at doses of 150, 300, and 600 microg x kg(-1) in rat, the serum PEG-rhGH concentration-time curves were fitted to a one-compartment model. The rhGH decorated by polyethylene glycol could prolong the action duration of rhGH in vivo, and reach the goal of long-action.

Efficacy of once-per-cycle administration pegylated recombinant human granulocyte colony-stimulating factor in chemotherapy-induced neutropenia in a phase I trial / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in the prophylaxis of chemotherapy-induced neutropenia.</p><p><b>METHODS</b>Patients with previously untreated non-small cell lung cancer or breast cancer and with normal bone marrow function were eligible for the trial. In the phase I trial, patients were to treated with two cycles of paclitaxel/carboplatin chemotherapy every 21 days. In cycle 1, if absolute neutrophil count (ANC) dropped below 1.0 x 10(9)/ L with fever and/or ANC dropped below 0.5 x 10(9)/L, rhG-CSF 150 microg/d was administrated until WBC > or = 10 x 10(9)/L or ANC > or = 5.0 x 10(9)/L. In cycle 2, patients were to receive a single injection of PEG-rhG-CSF (30, 60, 100, or 200 microg/kg) 48 hours after chemotherapy. Pharmacodynamic analyses were performed.</p><p><b>RESULTS</b>All the 16 patients enrolled (4 in each group) were eligible for efficacy evaluation. In cycle 1, 7 patients received rhG-CSF administration because of grade 4 neutropenia, while in cycle 2, there was only 1 episode of grade 4 neutropenia, which were in the 30 microg/kg group. In cycle 1, the mean ANC nadir of 1.37 x 10(9)/L occurred on day 13 in the 9 patients who received no rhG-CSF administration. In cycle 2, the mean ANC nadirs were 0.77 x 10(9)/L, 4.54 x 10(9)/L, 3.00 x 10(9)/L, and 5.56 x 10(9)/L, respectively, in 30, 60, 100, or 200 microg/kg group. The nadirs of the first two groups occurred on day 8 of cycle 2, while those of the other two groups appeared on day 7. After PEG-rhG-CSF administration, two mean ANC peaks were observed. The first one ranging from 20.87 x 10(9)/L to 33.61 x 10(9)/L in the 4 groups appeared on day 3 to day 4. In the 30 microg/ kg group, the mean ANC reached the second peak at 5.03 x 10(9)/L on day 14. The second peaks on day 10 in the other groups were 12.42 x 10(9)/L, 11.59 x 10(9)/L, and 18.92 x 10(9)/L, respectively. Pharmacodynamic analyses showed sustained serum concentrations of PEG-rhG-CSF during the period of neutropenia.</p><p><b>CONCLUSIONS</b>PEG-rhG-CSF administration may decrease the incidence of grade 4 neutopenia and result in earlier and higher nadir ANCs. PEG-rhG-CSF has a potential of once-per-cycle administration. The ANC and serum concentration of PEG-rhG-CSF are consistent with neutrophil receptor-mediated clearance.</p>