Equilibrium binding interactions between lotrafilcon a soft contact lenses and the two prostaglandin antiglaucoma drugs bimatoprost and tafluprost.

OBJECTIVES: To determine the equilibrium binding constant (EB) values of bimatoprost and tafluprost drug product formulations in contact with lotrafilcon A soft contact lenses and to characterize the importance of drug molecule hydrophobicity in controlling the binding interactions. METHODS: Bimatoprost Ophthalmic Solution and Tafluprost Ophthalmic Solution (Saflutan) were incubated with lotrafilcon A lens material for timed intervals at 25°C and 37°C. Aliquots were withdrawn, filtered, and tested using reverse-phase ultrahigh-performance liquid chromatography with respect to [bimatoprost] or [tafluprost] remaining in the solution. A series of homologous dialkyl phthalate esters and a series of homologous p-hydroxybenzoic acid alkyl esters were also tested as reference compounds. RESULTS: Bimatoprost and tafluprost were rapidly (within 15 min) absorbed from the solution by lotrafilcon A lenses, reaching an equilibrium within 60 min. At any lens:solution (w/v) ratio, the extent of drug binding to lens material was greater for tafluprost than for bimatoprost. The log(EB) values correlated with solute octanol:water partition coefficient (logP) values, indicating that hydrophobic interactions are important in controlling solute partitioning into the lens material. CONCLUSIONS: This study established the quantitative relationships between tafluprost and bimatoprost binding to lotrafilcon A lenses. The fraction of bimatoprost or tafluprost that binds to lotrafilcon A increases with increasing lens:solution (w/v) ratio. For a 60 µL dose volume applied to a single contact lens, 16% of initially present bimatoprost remains in the solution, whereas only 6% of initially present tafluprost remains in the solution. These calculations clearly demonstrate that both drugs partition extensively into lotrafilcon A contact lens material. Although the clinical implications of such binding can only be surmised, it would seem prudent to caution contact lens wearers to remove the lenses before administering either prostaglandin drug.

Formoterol fumarate and roxithromycin effects on muscle mass in an animal model of cancer cachexia.

Our study probed the effects of the beta-2 adrenergic agonist, formoterol and the macrolide antibiotic, roxithromycin, on muscle wasting in a well-characterized animal model of cancer cachexia. Female Wistar rats were inoculated with Yoshida AH130 ascites hepatoma (AH) cells to induce rapid and severe cachexia as demonstrated by wet weight determinations of the hearts, gastrocnemius muscles and carcasses. The control animals received saline (vehicle) inoculations. The AH-inoculated rats were treated once daily for four days by i.p. injection with a vehicle control, 1 mg/kg formoterol, 5 and 50 mg/kg roxithromycin or 1 mg/kg formoterol plus 5, 25, 40 and 50 mg/kg roxithromycin. The saline-inoculated animals were treated by i.p. injection with vehicle control, 1 mg/kg formoterol, 5 and 40 mg/kg roxithromycin. As a result, formoterol alone reduced the loss of muscle mass in the AH-inoculated rats by approximately one-half, consistent with literature reports. Roxithromycin alone at 5 mg/kg did not affect muscle mass in the AH-inoculated rats. Roxithromycin given alone at 50 mg/kg reduced the loss of muscle mass in AH-inoculated animals by approximately one-half. With respect to the antagonizing muscle loss, formoterol combined with either 5 or 25 mg/kg roxithromycin did not reach statistical significance versus formoterol alone, while formoterol plus either 40 or 50 mg/kg roxithromycin enhanced protection against muscle loss versus formoterol alone. The gastrocnemius weights in the AH-inoculated rats treated with formoterol combined with 40 mg/kg roxithromycin were not significantly different from the muscle weights in the saline-inoculated controls. To sum up, formoterol and roxithromycin apparently exert anti-cachectic effects in an additive fashion and may offer the potential for combination therapy in cachexia.