Abstract:

Objective To analyze the monitoring results of plasma-drug concentration of rifampicin in two different dosage forms and provide guidance for clinical proper drug use.Methods A hundred and thirty patients with active pulmonary tuberculosis (PTB), who received treatment in the Second Department of Tuberculosis of the Third People’s Hospital of Kunming from May 2016 to June 2017 were selected. Based on the principle of random number table, the enrolled patients were divided into an injection group (65 cases, rifampicin was given by intravenous drip, 0.6 g per time, once a day, with 500 ml 5% glucose injection) and an oral group (65 cases, rifampicin was administered orally, 0.6 g per time, once a day). The minimum inhibitory concentration (MIC) of rifampicin was 0.39-1.56μg/ml and the patients who reached the MIC of 0.39μg/ml were counted in this study. In the oral group, 2 patients were excluded because of the omission of the blood concentration monitoring data at different time points. So the study eventually included 128 patients, including 65 cases in the injection group and 63 cases in the oral group. After seven days of medication, plasma samples of the patients in two groups were collected in different time periods and the plasma-drug concentration of rifampicin in the two groups was tested by using UPLC-MS/MS.Results For the injection group, the highest concentration of rifampicin occurred at one hour and a half after injection, with a Median (Quartiles) (M (Q₁, Q₃)) of 0.954 (0.210, 3.420)μg/ml; for the oral group, it occurred at two hours after taking the medicine, with a Median (Quartiles) (M (Q₁, Q₃)) of 1.253 (0.249, 2.501)μg/ml. The peak and mean plasma-drug concentrations of rifampicin in the injection group were 1.786 (0.704, 3.591)μg/ml and 0.688 (0.269, 1.087)μg/ml, which were higher than those in the oral group (1.468 (0.423, 3.748)μg/ml and 0.571 (0.149, 1.894)μg/ml), but there was no statistical difference between the two groups (Z=-0.90 and -0.02; P=0.366 and 0.980). The valley plasma-drug concentration in the injection group (0.004 (0.001, 0.038)μg/ml) was lower than that in the oral group (0.007 (0.001, 0.070)μg/ml), and the difference between the two groups was a statistically significant (Z=-8.74, P=0.000). The total rate that the plasma-drug concentration reached MIC in the injection group was 47.7% (248/520) while that was 49.4% (218/441) in the oral group, there was no statistical difference between the two groups (χ ²=0.29, P=0.591).Conclusion The rifampicin treatment is given to the PTB patients either by injection or oral, the plasma-drug concentration of rifampicin all remains low. It fails to reach MIC in more than half of the patients and the internationally recommended reference range cannot be met. It may be coursed by inadequate dose. So he monitoring to the plasma-drug concentration of rifampicin should be strengthened and the use of rifampicin injection should be regulated.

Key words: Rifampin, Dosage forms, Administration, oral, Instillation, drug, Drug monitoring, Pharmacokinetics, Outcome assessment