38P - Study on human plasma concentration and serosal permeation of oral apatinib mesylate

Background

To explore the characteristics of plasma drug concentration and the possibility of drug passing through the serosa by oral administration of apatinib mesylate (APA-M, 250mg qd).

Methods

36 patients were included: lung adenocarcinoma (n=6), small cell lung cancer (n=12), gastric cardia adenocarcinoma (n=4), others (n=14). There were 5 patients with pleural effusions and 1 patient with peritoneal effusion. Plasma specimens of 36 patients were collected. At 7:40 am, fasting blood was drawn as plasma trough concentration (C_min). At 8 am, APA-M (250mg qd) was orally administrated. At 11 am, venous blood was drawn as plasma peak concentration (C_max). Each patient has C_min and C_max samples, and different patients have different amounts of samples. A total of 100 plasma samples were obtained. On the same day of plasma collection, 6 patients with serous cavity effusion were retained serous cavity catheter drainage. There were 13 pleural effusions samples (different patients have different amounts of samples) and 1 peritoneal effusion samples. The concentration of APA-M in plasma and serous cavity effusion was determined by UPLC-MS/MS.

Results

1) Steady-state of plasma drug concentration were achieved by day 4. The steady-state trough concentration (C_ss.min) and peak concentration (C_{ss. max}) was 357.7-727.6 ng/ml and 357.7-727.6 ng/ml, respectively. The average C_{ss. max} and C_ss.min was 528.3 ± 66.1 ng/ml and 276.9 ± 42.5 ng/ml, respectively. 2) APA can be detected in serous cavity effusion by day 2, and the effusion drug concentration was 3.14-84.5 ng/ml. After continuous administration for more than 10 days, the ratio of effusion to plasma was 12.7%-152.0%. The average amount of drug permeated in the effusion during each administration was 0.21-4.45 ug.

Conclusions

In clinical practice, the plasma drug concentration of APA reaches steady state quickly by oral administration (250mg qd) with small fluctuation range between peak and trough, and there is no significant drug accumulation during the long-term administration, which leads to a tolerable safety. APA can enter the effusion through the serosa, and the concentration of the drug has a cumulative trend, which can reach a higher drug concentration in the effusion finally.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.