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Aims Cysteamine is used to reduce tissue cystine content in patients suffering from nephropathic cystinosis. The objectives of the current study were to investigate pharmacokinetics and pharmacodynamics of cysteamine bitartrate in children and young adults with nephropathic cystinosis. Methods Cysteamine bitartrate was administered to 11 cystinosis patients at their regular dose level in a single-dose, open-label, steady-state study. Blood samples were collected and analysed for plasma cysteamine and white blood cell cystine content and pharmacokinetic and pharmacodynamic parameters estimated by NONMEM analysis using a linked pharmacokinetic-pharmacodynamic model. Results Cysteamine was rapidly cleared from the plasma (mean CL/F = 32.3 ml min -1 kg -1 , range = 17.3-52.2), appeared to be extensively distributed (mean V ss/F = 15.1 l, range 2.7-32.3) and exhibited a mean T max of 1.4 h. White blood cell cystine content post-dosing was significantly decreased compared with pre-and post-dose values (average decrement approximately 47%). A counter-clockwise hysteresis was noted in all patients, suggestive of a lag time (mean T lag = 0.44 h, range 0.22-0.92) between drug concentration and effect. Conclusions The results of this study establish that cysteamine is rapidly cleared from the plasma but that an every 6 h dosing interval adequately maintains white blood cell cystine content below the target of 1 nmol cystine per mg protein.

Lavender essential oil (LEO) is one the most favorite and widely used essential oils in aromatherapy. Many studies have demonstrated its functions in calming, assisting sleep, reducing pain and muscular spasms and its antiseptic function. To date, however, the mechanism of LEO on inflammation response is not well understood. In this study, we examined the effect of LEO on 5 μg/ml lipopolysaccharide (LPS) induced inflammation reaction in human monocyte THP-1 cells. We found treatment of 0.1% LEO significantly increased cell viability and inhibited the IL-1β and superoxide anion generation in LPS-stimulated THP-1 cells. Treatment with LEO down-regulated both LPS-induced protein levels of phospho-NF-κB and membrane Toll-like receptor 4. To determine whether the chaperone protein was involved in the reaction, we determined the levels of Heat Shock Protein 70 (HSP70). Our results showed that LEO increased HSP70 expression in LPS-stimulated THP-1 cells, suggesting that the LEO inhibited LPS-induced inflammatory effect might be associated with the expression of HSP70.

BACKGROUND: Nebivolol (N) is believed to be a unique cardiovascular agent studied worldwide for the treatment of HTN, CHF and other cardiovascular conditions owing to its vascular endothelial nitric oxide modulating capabilities and its highly selective ␤ 1antagonism. It is extensively metabolized with Ͻ0.1% of unchanged nebivolol excreted in urine. The present study examined what effect, if any, renal impairment has on oral N or its separate enantiomers.METHODS: Twenty-one subjects were divided into 3 renal impairment categories (mild, moderate, severe) based upon either measured (24-hour urine collection) or calculated (by Cockroft-Gault equation) creatinine clearance. Four healthy subjects, matched for age, gender, weight, and smoking habit, were selected as a control group.RESULTS: N (5 mg) was well tolerated with C max and T max being comparable across renal function classifications. Similar results were seen for the enantiomers and the active nebivolol glucuronide metabolites.

Background Nebivolol (N), which is considered to be an innovative cardiovascular agent that has been studied worldwide for the treatment of hypertension and CHF, undergoes extensive metabolism in humans to a variety of metabolites, some of which may contribute to its clinical activity. The effect of hepatic impairment on the single‐dose pharmacokinetics of N and its primary active glucuronide metabolites (G‐UD) was investigated. Methods Eight subjects with moderate hepatic impairment, based upon the Child‐Pugh Classification System, and eight healthy matched subjects each received a single 5 mg N dose. All subjects possessed CYP2D6 extensive metabolizer genotypes. Results N was well tolerated with Tmax being comparable between groups (see Table). Unlike N, G‐UD had a similar disposition between groups, with only t1/2 being statistically significantly different. Conclusions Based upon the statistically significant alteration in the pharmacokinetic disposition of N in moderate hepatically impaired subjects, dosage adjustment may be necessary in this population. Clinical Pharmacology & Therapeutics (2005) 77, P41–P41; doi: Parameter Normal Hepatic p‐value 90% CI AUC∞ (ng hr/ml)11.1848.990.0102.94–31.0Cmax (ng/mL)1.254.100.0121.65–5.85t1/2 (hr)7.4422.180.0052.24–4.24Cl/F (L/hr)1937168.20.0100–0.79