ABSTRACT
In recent years, monoclonal antibodies (mAbs) have been developing rapidly and widely used in fields of tumor, immunity, blood and other systemic diseases. Global share of mAbs in prescription drug market had reached up to $ 140 billion, 15.3% by 2019. As macromolecule proteins, with special structures and physiological properties, mAbs have great differences in absorption, distribution, metabolism and excretion in vivo compared with small molecule drugs, including characteristics of relatively large molecular mass, high specificity and selectivity in target combination, non-linear pharmacokinetics, time dependence, long half-life and so on. Fully understanding of these special pharmacokinetic characteristics shall effectively guide analysis of mAbs. Meanwhile, the particularity and complexity of disposal mechanism in organisms greatly increase the difficulty of biological detection. As a result, it is necessary to establish exclusive, sensitive, accurate and repeatable quantification methods in biological samples. This article focuses on pharmacokinetic characteristics, main analytical methods, and methodology validation of quantification for mAbs in biological samples, expounding with comparisons of small molecular drugs, so as to prompt development of pharmacokinetic study of this kind of drugs.
ABSTRACT
Objective To prepare asiatic acid (AA) loaded chitosan-deoxycholic acid self-assembled micelles (AA-CS-DCA PMs) adopting chitosan-deoxycholic acid (CS-DCA) as carriers and investigate its pharmacokinetic characteristics in rats. Methods AA-CS-DCA PMs were prepared by ultrasonic dispersion method. The characteristics of micelles were evaluated by the distribution of particle size, Zeta potential, drug loading, encapsulation efficiency, and in vitro release. Model of bile drainage was established in conscious rats and pre-column derivatization HPLC method was used to determine the concentration of AA in bile. Moreover, the pharmacokinetics characteristics of AA-CS-DCA PMs in vivo was evaluated by tmax, Cmax and AUC0-t. Results The particle size was (70.5 ± 9.8) nm, the Zeta potential was (38.4 ± 0.8) mV, and encapsulation efficiency and drug loading were (77.8 ± 1.2)% and (11.7 ± 0.2)%, respectively. The in vitro release profile showed a sustained release property. In vivo study showed that Cmax of AA-CS-DCA group (26.05 ± 3.04) μg/h was 2.8 times higher than that of the control group (9.19 ± 1.12) μg/h; The tmax of AA-CS-DCA PMs group prolonged significantly (P < 0.05) in biliary excretion (2 h vs 1 h) and the elimination half-life t1/2 was 1.8 times of the control group [(2.68 ± 1.71) h vs (1.49 ± 0.38 h)]. In addition, the AUC0-24 h which reflected the degree of drug absorption increased by 200% compared with the control group [(99.05 ± 12.83) μg vs (33.56 ± 8.33) μg]. Conclusion The chitosan- deoxycholic acid self-assembled micelles can raise the concentration of AA and prolong the retention time in vivo, which effectively improve the oral bioavailability of AA.