Toxicokinetic of phenothrin in rabbits

The toxicokinetics of single dose phenothrin were examined in rabbits. For this aim, a total of 14 New Zealand breed, 2 to 2.5 kg body weight, 6 month-old female rabbits were used. The animals were divided into two groups and each group had 7 animals. Phenothrin was administered intravenously to each animal in group 1, at a dose of 10 mg/kg b.w. and orally to each of the animals in group 2 at the same dose. Dimethyl sulfoxide was used as a solvent in application of phenothrin. Plasma phenothrin levels were measured by gas chromatography equipped with an ECD detector. Toxicokinetic evaluations were made according to the plasma phenothrin level-time curve. Phenothrin was found to be distributed according to the two-compartment open model. The values ​​of elimination half-life (t1/2β), mean residence time (MRT) and area under the curve (AUC0→∞) after intravenous phenothrin administration were 2.57 ± 0.10 h, 2.79 ± 0.09 h and 6893.05 ± 261.26 ng/h/mL, respectively. On the other hand, the maximum plasma concentration (Cmax), time to reach Cmax (tmax), t1/2β, MRT and AUC0→∞ after oral administration were 185.71 ± 8.21 ng/mL, 1.21 ± 0.20 h, 4.24 ± 0.39 h, 6.65 ± 0.54 h and 1054.04 ± 65.90 ng/h/mL, respectively. The oral bioavailability of phenothrin was calculated as 15.29%. Mean residence time was short and oral bioavailability was low. This may be one of the reasons why phenothrin is included in safe pesticides.

Population pharmacokinetics and Monte Carlo simulation for dosage optimization of fosfomycin in the treatment of osteoarticular infections in patients without renal dysfunction

Background: Fosfomycin is gaining interest in the treatment of complex osteoarticular infections (OI) due to MDR pathogens. Objective: The aims were to conduct population pharmacokinetics of fosfomycin in a cohort of OI patients receiving 16g/daily by intermittent (II) or continuous infusion (CI), and to carry out Monte Carlo simulations for dosage optimization in the treatment of these infections. Methods: Patients underwent blood sampling on day 5 of therapy (2-3 serial samples). Population pharmacokinetics and Monte Carlo simulations were performed to define the probability of target attainment (PTA) of 70% T>MIC, and the cumulative fraction of response (CFR) against common OI pathogens with dosages of 8, 12, 16, and 20g/day administered by II, extended-infusion (EI) or CI. Results: Forty-eight patients were recruited. A two-compartment open model with infusion input and first-order elimination was developed. Estimated creatinine clearance (CLCR) was included as covariate in the final model. Monte Carlo simulations showed that optimal PTAs and CFRs (≥90%) may be achieved in three different classes of renal function by administering a daily dosage of: 2g q6h by II against S. aureus, E. coli, ESBL-producing E. Coli and MRSA; 8g by CI against CoNS, K. pneumoniae and ESBL-producing K. pneumoniae; 12g by CI against P. aeruginosa, and 16g by CI against KPC-producing K. pneumoniae. Conclusion: Our study provides a strong rationale for considering fosfomycin dosages of 8-16 g daily by CI in several clinical scenarios for OI patients. Feasibility of administration by CI in an elastomeric pump makes fosfomycin a candidate for OPAT programs.

Availability, Pharmaceutics, Security, Pharmacokinetics, and Pharmacological Activities of Patchouli Alcohol

Patchouli alcohol (PA), a tricyclic sesquiterpene, is one of the critical bioactive ingredients and is mainly isolated from aerial part ofPogostemon cablin(known as guanghuoxiang in China) belonging to Labiatae. So far, PA has been widely applied in perfume industries. This review was written with the use of reliable information published between 1974 and 2016 from libraries and electronic researches including NCKI, PubMed, Reaxys, ACS, ScienceDirect, Springer, and Wiley-Blackwell, aiming at presenting comprehensive outline of security, pharmacokinetics, and bioactivities of PA and at further providing a potential guide in exploring the PA and its use in various medical fields. We found that PA maybe was a low toxic drug that was acquired numerously through vegetable oil isolation and chemical synthesis and its stability and low water dissolution were improved in pharmaceutics. It also possessed specific pharmacokinetic characteristics, such as two-compartment open model, first-order kinetic elimination, and certain biometabolism and biotransformation process, and was shown to have multiple biological activities, that is, immunomodulatory, anti-inflammatory, antioxidative, antitumor, antimicrobial, insecticidal, antiatherogenic, antiemetic, whitening, and sedative activity. However, the systematic evaluations of preparation, pharmaceutics, toxicology, pharmacokinetics, and bioactivities underlying molecular mechanisms of action also required further investigation prior to practices of PA in clinic.

Pharmacokinetics of lincomycin following intravenousadministration in febrile goats

Disposition of antimicrobials is known to be altered during disease conditions and fever is one of the common manifestations of bacterial infections in animals. The disposition of lincomycin (10 mg/kg, IV) during Echerichia coli endotoxin-induced fever in goats followed two compartment open model and drug was detected in plasma up to 8 h. The high AUC (39.5±6.21 mg.h/mL) indicated good antibacterial activity of lincomycin in goats. The volume of distribution and total body clearance were 3.35±0.45 L/kg and 0.28±0.03 L/h/kg, respectively. The long elimination half life 9.93± 2.83 h indicated persistence of drug for longer period in body. Lincomycin, is suggested to be repeated at 24 h interval for organisms sensitive to lincomycin having MIC up to 0.6 µg/mL for the treatment of bacterial infections manifested with fever in goats.

Effect of three anticoccidials on pharmacokinetics of tilmicosin in broiler chickens

The disposition kinetic of tilmicosin (25mg/kg) was studied following oral administration alone, pretreated with amprolium (240 ppm), pretreated with diclazuril (2.5 ppm) and pretreated with toltrazuril (25 ppm) in broiler chickens. The serum tilmicosin concentrations were determined by microbiological assay technique using Bacillus subtilis (ATCC 6633) as the test organism. Following oral administration of tilmicosin, the disposition curve was best described by two-compartment open model. The maximum serum concentration (Cmax) was 1.90 ± 0.11, 1.27 ± 0.13, 1.50 ± 0.14 and 1.41 ± 0.11µg/ml for tilmicosin alone and in the presence of amprolium, diclazuril and toltrazuril, respectively. The elimination half-life (T0.5 (el)) was significantly decreased (5.28 ± 0.30, 5.88 ± 0.33, 6.03 ± 0.25 h, respectively) in amprolium, diclazuril and toltrazuril pretreated broiler chicken compared to tilmicosin alone (7.30 ± 0.41 h). The outcomes illustrated a significant decrease in the interval between doses in amprolium, diclazuril and toltrazuril pretreated broiler chicken compared to tilmicosin alone. Amprolium diclazuril and toltrazuril, resulted in a significance decrease in AUC (12.02 ± 1.14, 15.50 ± 1.26 and 14.56 ± 1.46 µg.h.ml-1, respectively) compared to tilmicosin alone (21.98±1.83 µg.h.ml-1). It is concluded that the administration of amprolium, diclazuril and toltrazuril before tilmicosin would altered its pharmacokinetic profile in broiler chicken.

In VitroDissolution andIn VivoBioavailability of Six Brands of Ciprofloxacin Tablets Administered in Rabbits and Their Pharmacokinetic Modeling

This study was undertaken to assess thein vitrodissolution andin vivobioavailability of six brands of ciprofloxacin oral tablets available in the UAE market using rabbits. Thein vitrodissolution profiles of the six ciprofloxacin products were determined using the USP dissolution paddle method. Pharmacokinetic modeling using compartmental and noncompartmental analysis was done to determine the pharmacokinetic parameters of ciprofloxacin after single-dose oral administration.In vitrorelease study revealed that the amount of ciprofloxacin released in 20 minutes was not less than 80% of the labeled amount which is in accordance with the pharmacopoeial requirements. All tested products are considered to be very rapid dissolving except for formulae A and D. Ciprofloxacin plasma concentration in rabbits was best fitted to a two-compartment open model. The lowest bioavailability was determined to be for product A (93.24%) while the highest bioavailability was determined to be for product E (108.01%). Postmarketing surveillance is very crucial to ensure product quality and eliminating substandard products to be distributed and, consequently, ensure better patient clinical outcome. The tested ciprofloxacin generic products distributed in the UAE market were proven to be of good quality and could be used interchangeably with the branded ciprofloxacin product.

Pharmacokinetic study of isoquercitrin in rat plasma after intravenous administration at three different doses

The aim of this study is to develop a simple and specific HPLC method using vitexin as the internal standard to investigate the pharmacokinetics of isoquercitrin (ISOQ) after three different doses administrated intravenously to rats. The pharmacokinetic parameters were calculated by both compartmental and non-compartmental approaches. The results showed that ISOQ fitted a three-compartment open model. The values of AUC increased proportionally within the range of 5-10 mg·kg-1. Moreover, a half-life, b half-life, ªCL, MRT0-t and MRT0→∞ of ISOQ in rats showed significant differences between 20 mg·kg-1 and other doses, indicating that ISOQ presented dose-dependent pharmacokinetics in the range of 5-10 mg·kg-1 and non-linear pharmacokinetics at higher doses.

Simultaneous Determination of Volatile Constituents fromAcorus tatarinowiiSchott in Rat Plasma by Gas Chromatography-Mass Spectrometry with Selective Ion Monitoring and Application in Pharmacokinetic Study

A sensitive and specific gas chromatographic-mass spectrometry with selected ion monitoring (GC-MS/SIM) method has been developed for simultaneous identification and quantification ofα-asarone,β-asarone, and methyl eugenol ofAcorus tatarinowiiSchott in rat plasma. Chromatographic separation was performed on a Restek Rxi-5MS capillary column (30 m × 0.32 mm × 0.25 μm), using 1-naphthol as internal standard (IS). MS detection of these compounds and IS was performed atm/z178, 208, 208, and 144. Intra- and interday precisions of all compounds of interest were less than 10%. The recoveries are situated in the range of 92.4–105.2%. Pharmacokinetics of methyl eugenol confirmed to be one-compartment open model,α-asarone andβ-asarone was two-compartment open model, respectively. The method will probably be an alternative to simultaneous determination and pharmacokinetic study of volatile ingredients inAcorus tatarinowiiSchott.