A randomized comparison of pharmacokinetics of a single vaginal dose of dry misoprostol or misoprostol moistened with normal saline or with acetic acid

BACKGROUND: The pharmacokinetics of vaginal misoprostol as a dry tablet or as a tablet moistened with normal saline or with acetic acid were studied. METHODS: For this study, 42 women requesting termination of pregnancy at gestational age of <12 weeks were recruited and received 400 microg vaginal misoprostol tablets. They were randomized into three groups: (i) dry tablets, (ii) tablets moistened with 3 ml of normal saline and (iii) tablets moistened with 3 ml of 5% acetic acid. Venous blood samples were taken at 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min after misoprostol administration. Misoprostol acid (MPA) was determined in serum samples using gas chromatography/tandem mass spectrometry. RESULTS: The serum peak MPA concentration (C(max)) was significantly higher and the time-to-peak concentration (T(max)) was significantly shorter in the normal saline and acetic acid groups, when compared with the dry tablet group. Both areas under the curve at 240 and 360 min (AUC(240) and AUC(360)) of the normal saline and acetic acid groups were also significantly greater than that of the dry tablet group. The coefficients of variation in C(max) and T(max) were highest in the normal saline group, while that of AUC(240) and AUC(360) were highest in the dry tablet group. The C(max) was significantly higher in subjects in the dry tablet group with vaginal pH < 5 than in those with pH 5. There were no significant differences in other pharmacokinetic parameters between subjects with vaginal pH < 5 and those with vaginal pH 5 in all three groups. CONCLUSIONS: Vaginal misoprostol tablets moistened with normal saline or 5% acetic acid achieved better absorption than the dry tablet. The use of vaginal misoprostol tablets moistened with normal saline or 5% acetic acid would potentially improve the clinical efficacy of misoprostol. HKClinicalTrials.com registration: HKCTR-821.link_to_OA_fulltex

Biochemical Interaction Between Muscle and Bone: A Physiological Reality?

In elderly with a sedentary lifestyle, often suffering from sarcopenia to osteopenia, a training intervention could be an effective countermeasure for bone as well as muscle. Both bone and muscle adapt their mass and strength in response to mechanical loading in part via similar signaling pathways. Bone as well as muscle produces a wide variety of growth factors and cytokines in response to mechanical loading, which are important for their adaptations. It has been hypothesized that in addition to mechanical stimuli, muscle and bone communicate by these factors. Whether such biochemical interaction between both tissues is physiological is a still subject of debate. Here, we provide an overview of a range of biological factors possibly involved in the biochemical cross talk between bone and muscle. In addition, we discuss the plausibility that such interactions are involved in non-pathological adaptation of both tissues, either in paracrine or in endocrine fashion. As yet, convincing experimental evidence for biochemical cross talk between muscle and bone is very limited. Several studies have shown that muscle-derived factors are involved in bone fracture healing as well as in bone adaptation in case of muscle pathology. For involvement of cross talk between muscle and bone in physiological adaptation, there is no definite proof yet. Detailed knowledge of the biochemical interactions between muscle and bone is of clinical importance. It can help to discover pharmacological treatment to be used alone or in parallel with exercise training, thereby reducing the need for high-impact exercise. © 2014 Springer Science+Business Media New York