A Bidirectional Permeability Assay for beyond Rule of 5 Compounds.

Bidirectional permeability measurement with cellular models grown on Transwell inserts is widely used in pharmaceutical research since it not only provides information about the passive permeability of a drug, but also about transport proteins involved in the active transport of drug substances across physiological barriers. With the increasing number of investigative drugs coming from chemical space beyond Lipinski's Rule of 5, it becomes more and more challenging to provide meaningful data with the standard permeability assay. This is exemplified here by the difficulties we encountered with the cyclic depsipeptides emodepside and its close analogs with molecular weight beyond 1000 daltons and cLogP beyond 5.

Effect of benazepril, robenacoxib and their combination on glomerular filtration rate in cats.

Background: Combined use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs may induce acute kidney injury in humans, especially when combined with diuretics. The objective of this investigation was to evaluate the effects of benazepril, robenacoxib and their combination in healthy cats. In each of two studies (study 1 followed by study 2), 32 healthy cats were randomised to one of four groups (n = 4 male and 4 female cats per group) in a parallel-group design.

Influence of feeding schedules on the chronobiology of renin activity, urinary electrolytes and blood pressure in dogs.

The contribution of the renin-angiotensin-aldosterone system (RAAS) to the development of congestive heart failure (CHF) and hypertension (HT) has long been recognized. Medications that are commonly used in the course of CHF and HT are most often given with morning food for the sake of convenience and therapeutic compliance. However, biological rhythms and their responsiveness to environmental clues such as food intake may noticeably impact the effectiveness of drugs used in the management of cardiovascular disorders.

Chronobiology of the renin-angiotensin-aldosterone system in dogs: relation to blood pressure and renal physiology.

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the regulation of blood pressure and volume homeostasis. Its contribution to the development of cardiovascular diseases has long been recognized. Extensive literature has shown that peptides of the RAAS oscillate with a circadian periodicity in humans, under strong influence of posture, sleep, and age.

Growth hormone-releasing factor: structural modification or protection for more potent analogs.

Growth hormone-releasing factor was discovered in 1982 by Guillemin and has been subjected to intense investigations because of its huge potential applications. The major concerns encountered with the native molecules were their short half-lives in vivo in many species including man, precluding the practical use of these peptides for medical or production purposes. Many efforts to produce analogs of shorter length, more resistant to degradation and having higher affinity to the receptors have been made during the last decades.

Prevention and treatment of experimental osteomyelitis in dogs with ciprofloxacin-loaded crosslinked high amylose starch implants.

Crosslinked high amylose starch (CLHAS) matrix was used as a biodegradable drug delivery implant for the prevention and treatment of osteomyelitis. Thirty-two dogs underwent the femoral insertion of a screw inoculated with Staphylococcus aureus and were then randomly assigned to four groups: (A) prevention with ciprofloxacin-CLHAS implants, (B) surgical debridement (positive control), (C) surgical debridement and oral ciprofloxacin treatment and (D) surgical debridement and treatment with ciprofloxacin-CLHAS implants. At week 4 the osteomyelitis was confirmed, the infected site debrided and respective treatments initiated for groups B, C and D.

Tissue reaction and biodegradation of implanted cross-linked high amylose starch in rats.

The biocompatibility and degradation characteristics of cross-linked high amylose starch (Contramid were investigated in rats over 4 months. Contramid pellets (3-mm diameter and thickness) obtained by direct compression, were implanted subcutaneously and intramuscularly. On sequential time points, macroscopic observations of implantation sites were performed and tissue samples were removed, fixed, and histologically evaluated.

Characterization of crosslinked high amylose starch matrix implants. 2. In vivo release of ciprofloxacin.

The purpose of this study was to develop a crosslinked high amylose starch (CLHAS) matrix implant as a sustained antimicrobial delivery system for local prevention and/or treatment of osteomyelitis. Implants (200 mg) of CLHAS containing 2.5% (5 mg), 7.

Characterization of crosslinked high amylose starch matrix implants. 1. In vitro release of ciprofloxacin.

The objective of this study was to characterize in vitro the potential of crosslinked high amylose starch (CLHAS) as an implant matrix for the delivery of ciprofloxacin (CFX). Direct compression of dry blends of four different matrices: control CLHAS; CLHAS with 1% hydrogenated vegetable oil (HVO); and CLHAS with 10 or 20% hydroxypropylmethylcellulose (HPMC), each of them with three CFX loadings (2.5, 5.

Effects of pentoxifylline on pulmonary function and results of cytologic examination of bronchoalveolar lavage fluid in horses with recurrent airway obstruction.

Objectives: To determine the effects of pentoxifylline (PTX) administration on lung function and results of cytologic examination of bronchoalveolar lavage fluid in horses affected by recurrent airway obstruction (RAO).

Animals: 10 RAO-affected horses.

Procedures: 6 horses were orally administered PTX (16 g) mixed with corn syrup, and 4 horses were administered corn syrup alone, twice daily for 14 days.

Characterization of subcutaneous Contramid implantation: host response and delivery of a potent analog of the growth hormone-releasing factor.

Cross-linked high amylose starch (Contramid) was investigated as a solid implant for evaluation of host response in mice and as a possible delivery system for a human growth hormone-releasing factor analog (Hex-hGRF) release profile in pigs. Seventy mice were administered subcutaneously one 3 mm diameter Contramid pellet and host reaction was evaluated over 6 months. Thirty pigs were divided into four groups.