Current Issue : July-September Volume : 2025 Issue Number : 3 Articles : 5 Articles
Biancaea decapetala (Roth) O. Deg. (Fabaceae), traditionally used by the Hmong people to treat rheumatoid arthritis (RA), has not been extensively studied for the correlation between its anti-inflammatory activity and its active components. Protosappanoside D (PTD), a new component, has been isolated for the first time from the extract of Biancaea decapetala. This study focused on the anti-arthritic and anti-inflammatory effects of Biancaea decapetala extracts (BDE) and PTD, along with their pharmacokinetic–pharmacodynamic (PK-PD) analysis. In the adjuvant-induced arthritis (AA) rat model, HE staining and cytokine assays showed that BDE alleviated joint damage and reduced inflammatory cytokines, similar to the positive control. In the LPS-induced inflammatory cell model, both BDE and PTD demonstrated anti-inflammatory effects by inhibiting the secretion of inflammatory factors. A PK-PD analysis of BDE in AA rats and inflammatory cells, as well as an analysis of PTD as a monomer, was conducted. The results indicated that PTD had different regulatory effects on cytokines like TNF-α, with a certain lag and sustained effects. These findings suggest the potential of BDE and PTD as treatments for rheumatoid arthritis, though further in vivo studies and clinical trials are needed....
Background/Objectives: Risperidone ISM® is a long-acting injectable (LAI) formulation approved for monthly administration in schizophrenia treatment. It employs innovative in situ microimplant technology for biphasic drug release, achieving immediate and sustained therapeutic plasma concentrations without the need for oral supplementation or loading doses. This study evaluates the pharmacokinetic profile of Risperidone ISM® in a real-world clinical setting, focusing on plasma concentrations of the active moiety (Risperidone + 9-OH-Risperidone). Methods: An observational study was conducted to measure plasma concentrations of patients receiving Risperidone ISM® (75 mg or 100 mg). Samples were collected at pre-dose, 2 h, 24 h, 14 days, 21 days, and 25 days post-injection. Pharmacokinetic parameters, including Cmax, Cmin, Tmax, and AUC, were calculated and stratified by dose (75 mg and 100 mg) and injection site (gluteal vs. deltoid). Results: A total of 44 patients were included. Therapeutic plasma levels were reached within hours post-injection and sustained throughout the 28-day interval. Cmin values averaged 34.4 ng/mL and 36.1 ng/mL for the 75 mg and 100 mg doses, respectively. The median Tmax occurred at 24 h with a mean Cmax of 55.7 ng/mL and 59 ng/mL for 75 mg and 100 mg, respectively. Higher systemic exposure was observed for deltoid administration. Significant interindividual variability was noted, with 45.4% of patients exhibiting trough levels outside the therapeutic range. Conclusions: Risperidone ISM® achieves rapid and sustained therapeutic plasma levels, offering significant benefits in schizophrenia treatment. However, the high interindividual variability observed must be thoroughly studied, and the contributing factors identified to ensure the therapy is as effective and safe as possible....
Background/Objectives: Hypertensive disorders of pregnancy are a leading cause of pregnancy-related deaths in the United States, accounting for 7% of maternal mortality. Labetalol and nifedipine are the first-line drugs for the management of hypertension in pregnancy, but there are little data guiding the choice of one drug over the other. The current pilot longitudinal study aims to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of labetalol stereoisomers throughout pregnancy and postpartum. Methods: This is a single-center clinical study recruiting up to 40 pregnant individuals ≥ 18 years of age at the time of enrollment, taking labetalol as per the standard of care. The exclusion criteria include any pathophysiology impacting the PK of labetalol, e.g., liver failure. Maternal plasma, urine, amniotic fluid, cord blood, and breast milk will be collected, and labetalol stereoisomers will be measured using a validated LC-MS/MS assay. Heart rate and blood pressure will be measured as the PD endpoints. These may be assessed throughout a participant’s dosing interval at scheduled PK study visits, which will occur every 6–10 weeks during pregnancy, at delivery, during the 1st week postpartum, and up to 20 weeks postpartum. The primary aim is to characterize the PK and PD of labetalol during pregnancy and in the postpartum period. The secondary aim is to determine the extent of breast milk excretion of and infant exposure to labetalol from breast milk. The data will be analyzed using population PK modeling to evaluate the PK/PD relationship and ultimately develop trimester-specific dosing recommendations. Results/Conclusions: To our knowledge, this is the first study aiming to characterize the PK of labetalol stereoisomers across pregnancy and postpartum, utilizing individual stereoisomer data to evaluate the PK/PD relationship, and collecting postpartum samples, including breast milk, to model infant exposure to labetalol through breast milk. This study will provide important PK/PD data and knowledge which will be combined with large multi-center clinical trial data to develop trimester-specific dosing regimens for anti-hypertensive agents....
Background/Objectives: Doxycycline, a tetracycline-class antibiotic, is commonly used across various species to treat infections caused by susceptible bacteria. However, pharmacokinetic data on its use in alpacas remains limited. This study aimed to investigate the pharmacokinetics of doxycycline following intravenous (IV) and subcutaneous (SC) administration in alpacas. Methods: A randomized crossover study (n = 6) was employed, with dosages of 5 mg/kg and 20 mg/kg after intravenous and subcutaneous administration, respectively. Blood samples were collected at predetermined times up to 96 h after both routes of administration. Plasma doxycycline concentrations were determined using validated high-performance liquid chromatography with a UV detector and then analyzed based on non-compartmental pharmacokinetic methods. Results: All alpacas maintained optimal health and general condition throughout the trial period. After intravenous administration, the Vz value (0.90 L/kg) indicated a good distribution of this antibiotic in the alpacas. The maximum concentration value (Cmax) after SC administration of doxycycline was 1.40 μg/mL, reached at 1.92 h. Low bioavailability (F = 36.83%) of doxycycline was observed after SC administration. Conclusions: PK/PD ratios calculated from the pharmacokinetic data obtained, at a dose of 20 mg/kg and SC route of administration, suggest that doxycycline administered every 24 h could be effective against bacterial infections with MICs of 0.125 and 0.5 μg/mL. However, multi-dose and pharmacodynamic studies are needed to further evaluate the efficacy of using doxycycline in alpacas....
The aim of this study was to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of two insulin glargine preparations in healthy Chinese male subjects. Methods: Forty healthy Chinese male subjects were enrolled in this randomized, open, two-sequence, four-period, single-dose, crossover study and were randomly divided into RTRT or TRTR (first-period injection of test preparation, second-period injection of reference preparation, third-period injection of test preparation, fourth-period injection of reference preparation) groups. A 24 h euglycemic clamp test measured GIR. Plasma insulin glargine concentration and C-peptide were collected during the trial and analyzed by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) and enzyme-linked immunosorbent assay (ELISA). WinNonLin calculated PD/PK parameters and the equivalence of the two preparations was testified by SAS9.2. Results: The average concentration of C-peptide was lower than the baseline and the blood glucose was close to the targeted value in each sequence. PK parameters cmax of the test and the reference preparation insulin glargine were 0.580 and 0.614 ng·mL−1, and the AUC0–24h were 9.782 and 10.436 h·ng·mL−1, respectively. PD parameters GIRmax were 42.748 and 45.279 mg·kg−1·min−1, and AUCGIR,0–24h were 2.924 and 3.096 h·mg·kg−1·min−1, respectively. There was no clinically significant adverse reaction observed during the experiment. Conclusions: The glucose clamp has been established and bioequivalence between test preparation and reference preparation has been demonstrated....
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