Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction.

PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following intranasal administration in healthy male subjects and in Viagra-responsive erectile dysfunction (ED) patients. Erectile response was assessed by RigiScan trade mark in healthy subjects without visual sexual stimulation (VSS) and in Viagra-responsive ED patients with VSS. In healthy subjects, mean C(max) and AUC((0-t)) increased in a dose-dependent manner. Median T(max) was 0.50 h and mean t(1/2) ranged from 1.85 to 2.09 h. In both studies, an erectile response induced by PT-141 administration was statistically significant, compared to placebo, at doses greater than 7 mg, with the onset of the first erection occurring in approximately 30 min. PT-141 was safely administered and well tolerated in both studies. A maximum-tolerated dose was not identified. Flushing and nausea were the most common adverse events reported in both studies and no clinically significant changes in vital signs, laboratory tests, ECGs, or physical exams were observed. Based upon its erectogenic potential and tolerability profile, PT-141 is a promising candidate for further evaluation as a treatment for male ED.

Lack of oncogenicity of wood creosote, the principal active ingredient of Seirogan, an herbal antidiarrheal medication, in Sprague-Dawley rats.

Seirogan, an herbal medicine containing wood creosote (tablets, 10.0% w/w), has been developed and marketed for almost a century in various countries for the control of acute diarrhea and treatment of associated symptoms, such as abdominal cramping. Wood creosote (CAS no. 8021-39-4) is a mixture of simple phenolic compounds, including guaiacol and creosol and related compounds, and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. In the current study, the oncogenic potential of wood creosote was assessed in a 96/103-week oral gavage study in Sprague-Dawley rats. Groups of 60 rats/sex received wood creosote at dose levels of 20, 50, or 200 mg/kg body weight [bw]/day. An additional group of rats received the vehicle, 0.5% carboxymethylcellulose in deionized, distilled water, at the same dose volume as the treatment groups (10 ml/kg) and served as the controls. Treatment-related decreases in survival, body weight, and food consumption, as well as increased incidences of clinical signs that included rales, decreased activity, and salivation, were noted at 200 mg/kg bw/day when compared with the control group. There was an increased incidence of reddened and edematous lungs in rats from the 200 mg/kg bw/day group that died during the study. The lung findings were suggestive of test article aspiration during dose administration or agonal aspiration preceding and possibly resulting in death, especially because these observations were not seen in animals that survived to scheduled sacrifice. Additionally, phenols are generally recognized as having corrosive properties. There were no changes in clinical pathology and no increases in neoplastic or non-neoplastic lesions, excluding the lung findings, related to treatment with wood creosote at any dose level. Although the results of this study indicate that the maximum tolerated dose of wood creosote was met or exceeded at 200 mg/kg bw/day, there was no evidence of oncogenicity at any dose level. The lack of any evidence of oncogenicity supports the safety profile of the active ingredient in Seirogan, wood creosote.

Cost justification of clinical pharmacy services on a general surgery team: focus on diagnosis-related group cases.

We used a novel approach to cost-justify clinical pharmacy services on a general surgery team in nine diagnosis-related group cases. The clinical pharmacist monitored nine patients longitudinally on a general surgery team from admission to discharge and intervened in their therapeutic management. Each recommendation was analyzed for rationale, acceptance, perceived impact on quality and/or cost of patient care, whether self-initiated or solicited, and impact on patient outcome. Types of recommendations and outcomes were categorized by process and outcome measurement criteria. Total cost avoidance per patient was calculated using costs of drug therapy, laboratory tests, and length of stay. Accounting for cost of clinical pharmacy services, net cost avoidance per patient was calculated. The clinical pharmacist made 101 recommendations on nine patients. Physicians accepted 82 percent of the recommendations; 77 percent of the recommendations were self-initiated and 23 percent were solicited. Recommendations had a perceived impact on cost, quality, or both at 13, 31, and 56 percent, respectively. Most recommendations (79 percent) brought patient therapy to a level of conformance with current standards of practice as documented in the medical literature. Recommendations that potentially preserved a major organ function by preventing drug-induced toxicity or the exacerbation of existing problems constituted 16 percent of the total. None of the accepted recommendations adversely affected patient outcome and 23 percent directly resulted in a measurable positive outcome in patient care. A total of four hospital days was potentially saved for two cases. Based on objective outcome criteria, a 1.9-day increase in therapeutic control was documented per patient.(ABSTRACT TRUNCATED AT 250 WORDS)