Herb-Drug Interaction Between Xiyanping Injection and Lopinavir/Ritonavir, Two Agents Used in COVID-19 Pharmacotherapy

The global epidemic outbreak of the coronavirus disease 2019 (COVID-19), which exhibits high infectivity, resulted in thousands of deaths due to the lack of specific drugs. Certain traditional Chinese medicines (TCMs), such as Xiyanping injection (XYPI), have exhibited remarkable benefits against COVID-19. Although TCM combined with Western medicine is considered an effective approach for the treatment of COVID-19, the combination may result in potential herb-drug interactions in the clinical setting. The present study aims to verify the effect of XYPI on the oral pharmacokinetics of lopinavir (LPV)/ritonavir (RTV) using an in vivo rat model and in vitro incubation model of human liver microsomes. After being pretreated with an intravenous dose of XYPI (52.5 mg/kg) for one day and for seven consecutive days, the rats received an oral dose of LPV/RTV (42:10.5 mg/kg). Except for the t1/2 of LPV is significantly prolonged from 4.66 to 7.18 h (p < 0.05) after seven consecutive days pretreatment, the pretreatment resulted in only a slight change in the other pharmacokinetic parameters of LPV. However, the pharmacokinetic parameters of RTV were significantly changed after pretreatment with XYPI, particularly in treatment for seven consecutive days, the AUC0-∞ of RTV was significantly shifted from 0.69 to 2.72 h μg/mL (p < 0.05) and the CL exhibited a tendency to decrease from 2.71 L/h to 0.94 L/h (p < 0.05), and the t1/2 of RTV prolonged from 3.70 to 5.51 h (p < 0.05), in comparison with the corresponding parameters in untreated rats. After administration of XYPI, the expression of Cyp3a1 protein was no significant changed in rats. The in vitro incubation study showed XYPI noncompetitively inhibited human CYP3A4 with an apparent Ki value of 0.54 mg/ml in a time-dependent manner. Our study demonstrated that XYPI affects the pharmacokinetics of LPV/RTV by inhibiting CYP3A4 activity. On the basis of this data, patients and clinicians can take precautions to avoid potential drug-interaction risks in COVID-19 treatment.

Evaluation of a Tasteless Enrofloxacin Pharmaceutical Preparation for Cats. Naive Pooled-Sample Approach to Study Its Pharmacokinetics

Available pharmaceutical preparations of enrofloxacin injected SC or IM to cats are likely to cause adverse tissue reactions in the injection sites (pH of the drug preparations is ≥10.4). Tablets often induce abundant ptyalism and vomiting, casting doubt on the efficacy of the drug administration maneuver. In addition, the reported oral bioavailability is very low. In this trial, the oral pharmacokinetics of dried alginate beads of enrofloxacin (DABE) administered by concealing them in the cat’s moist food or morsels, is described. A naïve polled sampling approach was chosen with fourteen adult healthy cats. Neither their housing nor their feeding habits were altered. A single pharmacokinetic profile was obtained with 5 samples per designated bleeding time, sampling each cat 2–3 times only. None of the cats rejected their medicated food or morsels. Plasma profile of enrofloxacin exhibited an AUC0–24 value of 12.4 µg·h/mL and an AUC0–∞ value of 19.2 µg·h/mL, which are comparatively greater than values previously referred for kittens. In contrast, λ and elimination t½ were almost identical (0.12 1/h and 6.1 h). Pharmacokinetics/pharmacodynamics ratios taking the breakpoint of Staphylococcus epidermidis as a surrogate (0.5 µg/mL), can be regarded as borderline or low, but perhaps adequate in cats, as higher concentrations may be linked to toxicity (AUC0–24/MIC = 24.8; Cmax/MIC = 4.6).

A simple, precise, and sensitive HPLC method for quantification of letrozole in rat plasma: development, validation, and preclinical pharmacokinetics

A simple bioanalytical liquid chromatographic method was developed and validated to quantify letrozole (LTZ) in rat plasma. Protein precipitation using acidified chilled acetonitrile (containing 0.1% orthophosphoric acid) was used to extract LTZ from the plasma. Chromatographic separation was carried out on Kinetex C18 reverse phase (RP) column (250 mm × 4.6 mm i.d., 5 μm) using a mixture of 20 mM acetate buffer (pH 5.5) and acetonitirile (60:40 %v/v) eluting at 1.0 mL/min flow rate with the method responses measured at 240 nm. The optimized method was selective and established good linearity with recovery ranging between 91.16 and 99.44%. The validation experiments revealed that the method showed acceptable precision (2.61–7.48%) and accuracy (97.44–102.70%) and was found to be stable. The sensitivity of the method was demonstrated by the lowest concentration (LLOQ) detected at 75 ng/mL. Using the developed method, single-dose oral pharmacokinetics in Sprague-Dawley rats was carried out to successfully confirm the applicability of the method for the quantification of LTZ in biological matrix.