Objective:To determine the potential drug-drug interactions between anti-malarial candidate 97/78 and anti-tubercular drug rifabutin in-vivo in rats followed byin-vitro investigation of the underlying mechanisms of drug interaction.Methods: Single oral dose study was conducted in male and female rats at 40 mg/kg and 70 mg/kg for 97/78 and rifabutin respectively. Results:It was reported that rifabutin co-administration altered pharmacokinetics of 97/63 (active metabolite of 97/78). A significant decrease was reported in the systemic exposure of 97/63 by a factor of 3-4. The AUC0-last values were (4.03 ± 0.60) and (5.44 ± 1.15) μg?h?mL-1 upon 97/78 administration alone, while the values were decreased to (1.13 ± 0.10) and (1.23 ± 1.13) μg?h?mL-1 upon rifabutin co-administration in male and female rats respectively. Statistically significant differences were also reported in Cmaxand Tmax values upon rifabutin co-administration.In-vitro drug metabolism study in rat liver microsomes has shown that the metabolism of 97/63 was increased by 10%-12% upon rifabutin co-incubation. The extent of plasma protein binding of 97/63 was found to be decreased from 54%-55% to 6%-8% upon rifabutin addition.Conclusions:It was concluded that rifabutin co-administration altered PK parameters of 97/63 in SD rats. However, no intersex influences were reported in the interaction pattern. The results obtained in the in-vivo study were well correlated with thein-vitro findings and can further be applied to explore other aspects of potential drug interactions between these two drugs.

Objective: To determine the potential drug-drug interactions between anti-malarial candidate 97/78 and anti-tubercular drug rifabutin in-vivo in rats followed by in-vitro investigation of the underlying mechanisms of drug interaction. Methods: Single oral dose study was conducted in male and female rats at 40 mg/kg and 70 mg/kg for 97/78 and rifabutin respectively. Results: It was reported that rifabutin co-administration altered pharmacokinetics of 97/63 (active metabolite of 97/78). A significant decrease was reported in the systemic exposure of 97/63 by a factor of 3-4. The AUC0-last values were (4.03 ± 0.60) and (5.44 ± 1.15) μg h mL^-1 upon 97/78 administration alone, while the values were decreased to (1.13 ± 0.10) and (1.23 ± 1.13) μg h mL^-1 upon rifabutin co-administration in male and female rats respectively. Statistically significant differences were also reported in Cmax and Tmax values upon rifabutin co-administration. In-vitro drug metabolism study in rat liver microsomes has shown that the metabolism of 97/63 was increased by 10%-12% upon rifabutin co-incubation. The extent of plasma protein binding of 97/63 was found to be decreased from 54%-55% to 6%-8% upon rifabutin addition. Conclusions: It was concluded that rifabutin co-administration altered PK parameters of 97/63 in SD rats. However, no intersex influences were reported in the interaction pattern. The results obtained in the in-vivo study were well correlated with the in-vitro findings and can further be applied to explore other aspects of potential drug interactions between these two drugs.

PURPOSE: To compare the efficacy and safety of latanoprost, bimatoprost, travoprost and timolol in reducing intraocular pressure (IOP) in patients with primary open angle glaucoma. METHODS: This was a prospective study conducted at a tertiary-care centre. One hundred and forty patients with newly diagnosed primary open angle glaucoma were randomly assigned to treatment with latanoprost (0.005%), bimatoprost (0.03%), travoprost (0.004%) or timolol gel (0.5%); 35 patients were assigned to each group. All patients were followed for 2, 6, and 12 weeks. The main outcome measure studied was the change in IOP at week 12 from the baseline values. Safety measures included recording of adverse events. RESULTS: The mean IOP reduction from baseline at week 12 was significantly more with bimatoprost (8.8 mmHg, 35.9%) than with latanoprost (7.3 mmHg, 29.9%), travoprost (7.6 mmHg, 30.8%) or timolol (6.7 mmHg, 26.6%) (ANOVA and Student's t-tests, p < 0.001). Among the prostaglandins studied, bimatoprost produced a maximum reduction in IOP (-2.71; 95% confidence interval [CI], -2.25 to -3.18) followed by travoprost (-1.27; 95% CI, -0.81 to -1.27) and latanoprost (-1.25; 95% CI, -0.79 to -1.71); these values were significant when compared to timolol at week 12 (Bonferroni test, p < 0.001). Latanoprost and travoprost were comparable in their ability to reduce IOP at each patient visit. Ocular adverse-events were found in almost equal proportion in patients treated with bimatoprost (41.3%) and travoprost (41.9%), with a higher incidence of conjunctival hyperemia (24.1%) seen in the bimatoprost group. Timolol produced a significant drop in heart rate (p < 0.001) at week 12 when compared to the baseline measurements. CONCLUSIONS: Bimatoprost showed greater efficacy when compared to the other prostaglandins, and timolol was the most efficacious at lowering the IOP. Conjunctional hyperemia was mainly seen with bimatoprost. However, the drug was tolerated well and found to be safe.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antihypertensive Agents/adverse effects/*therapeutic use ; Bimatoprost/adverse effects/therapeutic use ; Blood Pressure/drug effects ; Female ; Glaucoma, Open-Angle/*drug therapy/physiopathology ; Heart Rate/drug effects ; Humans ; Intraocular Pressure/drug effects ; Male ; Middle Aged ; Prostaglandins F, Synthetic/adverse effects/therapeutic use ; Timolol/adverse effects/therapeutic use ; Tonometry, Ocular ; Travoprost/adverse effects/therapeutic use ; Treatment Outcome ; Visual Acuity/drug effects ; Visual Field Tests ; Visual Fields/drug effects

Sudden ascent to high altitudes beyond 2,438 m can cause life-threatening complications such as acute mountain sickness and high altitude cerebral and pulmonary oedema. We present a case of pituitary apoplexy in a young man who ascended to high altitude gradually, after proper acclimatisation. He developed headache, nausea, vomiting and persistent hypotension. Magnetic resonance imaging revealed an enlarged pituitary gland with haemorrhage. His hormonal estimation showed acute adrenal insufficiency due to corticotropin deficiency. The patient responded well to conservative medical management with hormonal replacement therapy. This is most likely the first reported case of high altitude-induced pituitary apoplexy in the literature.
Acclimatization ; Adrenal Insufficiency ; complications ; Adrenocorticotropic Hormone ; deficiency ; Adult ; Altitude ; Altitude Sickness ; complications ; Brain ; pathology ; Hormone Replacement Therapy ; methods ; Humans ; Hypotension ; physiopathology ; Intracranial Hemorrhages ; physiopathology ; Magnetic Resonance Imaging ; methods ; Male ; Pituitary Apoplexy ; diagnosis ; etiology ; Pituitary Gland ; physiopathology

Aged ; Bendamustine Hydrochloride ; therapeutic use ; Humans ; Lymphadenopathy ; diagnosis ; Lymphoma ; diagnosis ; drug therapy ; Male ; Rituximab ; therapeutic use