Background/Objectives: An extract of calyces from Physalis peruviana with hypoglycemic activity is being considered as a potential herbal medicine. Preclinical pharmacokinetics (PK) studies of the extract in rats, focusing on plasma concentrations of its main compound, rutin, and its metabolites, revealed PK interactions in the extract matrix that improved the absorption of rutin metabolites compared to the pure compound, among other PK effects. This research aimed to study the PK of rutin alone and in the extract and assess potential PK interactions in the extract matrix on the flavonoid and its metabolites in rabbits, a nonrodent species; Methods: Animals received pure rutin or extract orally and intravenously. The PK analysis used noncompartmental and population pharmacokinetics (popPK) methods, and simple allometry was applied to predict human PK parameters; Results: The rutin concentration–time profile fit a two-compartment model with first-order elimination, while its metabolites fit a double first-order absorption model. The extract matrix led to increased absorption, distribution, and elimination of rutin as well as increased bioavailability of its metabolites in rabbits; Conclusions: The popPK model defined the equations for PK parameters describing these findings, and the increased volume of distribution and clearance of rutin was maintained in human predictions. These results will support the development of a new herbal medicine.
1 January 2025 in Journal of the Brazilian Chemical Society
Acquired immunodeficiency syndrome is an infectious disease caused by human immunodeficiency virus (HIV). Pharmacological antiretroviral therapy, along with therapeutic monitoring of drug plasma concentrations, facilitates adequate and effective follow-up in each patient. Our main objective was to develop and validate a high-performance liquid chromatography with ultraviolet detector (HPLC-UV) bioanalytical method for the simultaneous quantification of plasma concentrations of three commonly used antiretrovirals in Colombia: efavirenz, lopinavir, and ritonavir. This method is intended for therapeutic drug monitoring in persons living with HIV locally or in developing countries. The method is selective, specific, accurate, precise, and stable over the concentration range of 250 and 20,000 ng mL-1 for the drugs. It was successfully applied to measure the plasma levels of efavirenz, lopinavir, and ritonavir in HIV patients, which ranged from 251.0 ± 10.4 to 7186.2 ± 10.2, 8188.2 ± 5.9 to 15,312.5 ± 6.6, and 246.1 ± 6.5 to 1189.0 ± 6.4 ng mL-1, respectively.
Vancomycin (VCN) is a glycopeptide antibiotic widely used to treat Gram-positive infections such as those caused by methicillin-resistant Staphylococcus aureus (MRSA). Its narrow therapeutic window, high interindividual pharmacokinetic variability, and dose-dependent nephrotoxicity support the need for therapeutic drug monitoring (TDM). In this study, a UHPLC-UV method for VCN quantification in human plasma was developed and validated according to ICH M10 guidelines, using a one-step protein precipitation requiring only 100 µL of plasma. Clinical applicability was preliminarily explored in three hospitalized patients, where the area under the concentration-time curve over 24 h to minimum inhibitory concentration ratio (AUC24/MIC) was estimated using PrecisePK, NextDose, and TDMx Bayesian software platforms before and after dose adjustment. The method showed linearity from 0.5 to 100 µg/mL (r2 > 0.99), with accuracy within ±7% and precision below 11%. Acceptance criteria for selectivity and matrix effect were met, and stability was confirmed under multiple conditions, including clinically relevant storage and transport. Pre-adjustment AUC24/MIC values were outside the target window of 400–600 in all patients, confirming the pertinence of implementing model-informed precision dosing as a routine TDM practice in Colombian health institutions.