A Single Dose of Baicalin Has No Clinically Significant Effect on the Pharmacokinetics of Cyclosporine A in Healthy Chinese Volunteers

Abstract

Despite its narrow therapeutic window and large interindividual variability, cyclosporine A (CsA) is the first-line therapy following organ transplantation. Metabolized mainly by CYP3A and being a substrate of P-glycoprotein (P-gp), CsA is susceptible to drug–drug interactions. Baicalin (BG) is a drug used for adjuvant therapy of hepatitis in traditional Chinese medicine. Since its aglycone baicalein (B) inhibits CYP3A and P-gP, co-administration might affect CsA pharmacokinetics. This study investigated the effect of BG on CsA pharmacokinetics. In a two-period study, 16 healthy volunteers received a single 200 mg oral CsA dose alone (reference period) or in combination with 500 mg BG (test period). Pharmacokinetic evaluation of CsA was carried out using non-compartmental analysis (NCA) and population pharmacokinetics (popPK). Treatments were compared using the standard bioequivalence method. Based on NCA, 90% CIs of AUC and C max test-to-reference ratios were within bioequivalence boundaries. In the popPK analysis, a two-compartment model (clearance/F 62.8 L/h, central and peripheral volume of distribution/F 254 L and 388 L) with transit compartments for absorption appropriately described CsA concentrations. No clinically relevant effect of 500 mg BG co-administration on CsA pharmacokinetics was identified and both treatments were well tolerated.

A simple and accurate LC‑MS/MS method for monitoring cyclosporin A that is suitable for high throughput analysis

“…For managing the patient's condition and preventing complications, ISD treatment among patients with nephropathy is frequently combined with corticosteroids, anti-hypertensives, or lipid-modifying drugs. From a metabolic perspective, the CSA concentrations in patients with different drug combinations might yield different results, owing to drug-drug interactions ( 5 , 29 ). In this study, the CSA concentrations detected by using the LC-MS/MS method were compared with those detected by other methods presented in previous studies in patients with NS or kidney transplants receiving the same drug combinations ( 30-33 ) ( Table VII ).…”

“…Notably, the complicated purification process is time-consuming and technically challenging (because of personnel requirements, quality control for the overall process, and auxiliary equipment demands). Protein precipitation (PPT), liquid-liquid extraction (LLE), and solid-phase extraction (SPE) are most frequently used for blood CSA preparation (5)(6)(7)(8)(9)21). Compared to existing protein precipitation methods, the sample preparation procedure often contains multiple liquid-adding and mixing steps (Table Ⅵ).…”

“…LC-MS/MS combines the separation efficiency of HPLC with the high sensitivity of MS, although ease of use remains a challenge. Certain LC-MS/MS methods require cumbersome pretreatment steps, commonly using a multi-step protein precipitation procedure, liquid-liquid extraction methods, and solid-phase extraction (5)(6)(7)(8)(9). Both the time and cost of sample pretreatment and the long separation time together limit the throughput of LC-MS/MS, especially for those with a single liquid chromatography system with a long running time.…”

Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

“…One aspect of the use of such medicines that requires close attention is how to achieve synergy and greater effects but at low doses. Pharmacokinetics can play a key role in the evaluation of drug effects [42], drug-dosing intervals, etc., and is considered an efficient means of elucidating the mechanism of herbal formulas [43].…”

Drug Development for the Management of Corona Viruses: Insights from Natural Antiviral Agents

“…Moreover, baicalin capsules (250 mg per capsule) is an approved drug by the state food and drug administration of China as an adjuvant therapy for managing hepatitis. 93…”