Current Issue : April-June Volume : 2026 Issue Number : 2 Articles : 5 Articles
Background: In Europe, Vipera ammodytes ammodytes (Vaa, nose-horned viper) is considered the most venomous of the European vipers. The antivenom Viperfav®, composed of polyvalent equine F(ab)2 fragments, is effective against Vipera aspis, Vipera berus and Vaa. Objectives: This study aimed to evaluate the clinical efficacy and pharmacokinetics of Viperfav in Vaa envenomations. Methods: Patients presenting with Vaa snakebite and treated with intravenous Viperfav were included. Clinical manifestations and laboratory findings were assessed on admission to the Emergency Department, prior to antivenom therapy, and monitored throughout hospitalization. Blood samples were collected on arrival and at defined intervals after Viperfav administration. Venom and antivenom concentrations in serum were determined by ELISA and subjected to pharmacokinetic analysis. Results: Twenty-one patients bitten by Vaa and classified with a severity score of 2b on the modified Audebert clinical severity scale received a single intravenous dose of Viperfav within 4 h of the bite. Viperfav attenuated the progression of local symptoms and prevented the development of new systemic manifestations. The serum concentrations of F(ab)2 fragments reached 196 μg/mL, far exceeding the venom concentration at admission (35 ng/mL). The prolonged elimination half-life of Viperfav (49 h) corresponded with the absence of recurrent symptoms after a single dose. Bradycardia or hypotension occurred in 10% of patients; no cases of anaphylaxis or serum sickness were observed. Conclusions: A single intravenous dose of Viperfav demonstrated clinical efficacy and a favourable pharmacokinetic profile in Vaa envenomed patients when administered within hours of the bite....
Purpose: The Amsterdam UMC pharmacy has been compounding chenodeoxycholic acid (CDCA) capsules for Dutch cerebrotendinous xanthomatosis patients since 2018. However, limited data are available on the pharmacokinetics and bioequivalence of therapeutic CDCA formulations. Methods: An open-label, single-center, randomized, two-period, twosequence, cross-over study was conducted in 12 healthy volunteers to compare the pharmacokinetic profile of pharmacy-compounded CDCA capsules to that of the authorized CDCA product. Results: Both formulations reached peak plasma concentrations (tmax) at approximately 1 h post-dose. The mean AUC(0–6h) values were 262.4 (±69.4) μmol·min/L for the compounded capsules and 248.0 (±78.1) μmol·min/L for the authorized capsules, with a 90% confidence interval (CI) for the AUC(0–6h) ratio of 0.89–1.30, exceeding the accepted bioequivalence range of 0.80–1.25. The mean Cmax for the compounded formulation (2.96 ± 0.91 μmol/L) was significantly lower than that of the comparator product (4.42 ± 1.36 μmol/L; p = 0.0040), with a 90% CI for the Cmax ratio of 0.57–0.80, also outside the bioequivalence range. Conclusions: Overall, the pharmacy-compounded and authorized capsules demonstrate a comparable AUC(0–6h) and tmax. Bioequivalence could not be demonstrated, primarily due to high variation, a significantly lower Cmax, and an AUC(0–6h) ratio outside the accepted limits. These findings indicate that the compounded formulation results in reduced systemic peak exposure compared with the authorized product. However, given the high variation, a larger sample size would be needed to further investigate bioequivalence in future studies....
Introduction: Cannabis holds therapeutic potential; however, activation of the type 1 cannabinoid receptor (CB1R) via Δ9-tetrahydrocannabinol (THC) is also responsible for the characteristic “high” induced by cannabis. The pharmacology of the less abundant phytocannabinoid, cannabigerol (CBG), is poorly established, though it has been shown to exhibit promising therapeutic properties such as potential anxiolytic effects. Methods: We assessed the pharmacokinetics (PK) and pharmacodynamics (PD) of CBG in C57BL/6Crl mice, hypothesizing that CBG would produce fewer PD effects than we had previously observed with THC, even when accounting for PK differences. Following oral (p.o.), intraperitoneal (i.p.), and intravenous (i.v.) administration, the PK profile of CBG was assessed via blood sampling at specified time points (10 min, 30 min, 1 h, 3 h, 6 h, 12 h, 18 h, and 24 h). The blood concentrations of CBG were quantified by High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS). A separate cohort of mice was treated with CBG and tested for cataleptic, hypothermic, anti-nociceptive, and locomotor effects to correlate the PK profile of CBG with CBG’s observed PD effects. Results and Discussion: Our data reveal that CBG was not intoxicating, even when accounting for the route of administration and blood concentration. Our findings support previous reports that CBG is not intoxicating and reveal that even if CBG were present at sufficiently high concentrations in cannabis products, it would not produce intoxicating effects like those of THC....
Background: Physiologically based pharmacokinetic (PBPK) modeling is applied to address clinical pharmacology issues including dose selection and exposure assessments for special populations (e.g., pediatrics, and renally or hepatically impaired patients). The objective of this study was to evaluate the predictive performance of a PBPK model for dosing assessment of intravenous immunoglobulin (IVIG) and anti-D immunoglobulin (anti-D Ig) products in pregnant women. Methods: A minimal PBPK (mPBPK) model that incorporates pregnancy-specific physiological parameters and allometric scaling approaches was developed and evaluated for predicting the exposure of IVIG and anti-D Ig in pregnant women. The concentration versus time data were obtained from the published literature. Results: The IVIG (n = 22) and anti-D Ig (n = 29) concentrations were predicted using the mPBPK model with an average fold error of 1.17 and 1.22, respectively. A total of 100% and 95% of IVIG concentrations were predicted within the 0.5–2-fold and 0.5–1.5-fold prediction error ranges, respectively. For anti-D Ig, predictions fell within the 0.5–2-fold and 0.5–1.5-fold ranges for 93% and 76% concentrations, respectively. A mPBPK model-based simulation following administration of 0.5 g/kg IVIG in 100 virtual nonpregnant and pregnant subjects revealed that the maximum plasma concentration (Cmax) was 15% lower and trough concentration (Ctrough) was 8% lower during the third trimester of pregnancy compared to nonpregnant subjects. In contrast, with flat dosing, Cmax and Ctrough were 32% and 26% lower in pregnant subjects, respectively. Overall, the model demonstrated reasonable predictive performance, and bodyweight-based dosing regimen is an acceptable approach that results in minimal change in exposure of IVIG in pregnant women....
Background/Objectives: Ulcerative colitis (UC), a chronic inflammatory bowel disease, affects approximately 5 million individuals worldwide, exerting a considerable influence on global health and economic systems. Among the challenges in UC management, treatment non-adherence stands out as a critical issue, often compromising therapeutic efficacy. One strategy to address this challenge is by reducing pill burden, which may improve patient compliance and optimize treatment outcomes. Methods: This randomized, twosequence, four-period, crossover replicate study evaluated the pharmacokinetic profiles, bioequivalence, and safety of a newly developed 1500 mg mesalazine gastro-resistant tablet compared to three of the reference 500 mg Claversal® gastro-resistant tablets (total dose 1500 mg) in 80 healthy participants under fasted conditions. Results: Bioequivalence between mesalazine formulations was observed in both the rate and extent of systemic bioavailability. The geometric mean ratios and their 90% CI were 102.51% (95.85–109.63) for AUC0–∞, 103.36% (96.40–110.83) for AUC0–t, 84.49% (78.24–91.24) for AUC8–48h, and 114.24% (100.15–130.32) for Cmax. All within the accepted bioequivalence ranges, confirming comparable pharmacokinetic performance. Secondary pharmacokinetic parameters such as tmax, t1/2, Ke, Cl, and MRT were also consistent across both formulations. The incidence of adverse events was comparable between the two mesalazine formulations, with only flatulence and mild self-limited rash considered possibly related to test treatment. Conclusions: Overall, the 1500 mg formulation demonstrated a pharmacokinetic profile and tolerability comparable to the reference formulation, offering a higher-strength option to reduce daily pill burden. This strategy is of clinical relevance, particularly for improving treatment adherence among UC patients who need to take multiple pills daily to achieve their required dosage. While adherence is influenced by various factors, reducing pill burden may facilitate compliance and optimize therapeutic efficacy....
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