Immunoassay-based measurement of clinical biomarkers for monitoring changes in nasal cavity.

BACKGROUND: Many drugs for treatment of allergies, migraine headaches, inflammation, and other indications are administered into the nasal cavity providing access to the immune and central nervous systems. One of the concerns for using this route of administration is potential damage to the nasal epithelium and mucosal regions. We assembled a panel of clinical biomarkers that can be used to monitor changes in the nasal epithelium, mucosa, and olfactory regions in preparation for clinical trials involving drugs administered via intranasal route. These biomarkers included albumin, elastase, IL-6, IL-8, lactoferrin, myeloperoxidase and nerve growth factor. METHODS: Immunoassays were developed and used to measure changes in these biomarkers in nasal lavage samples collected twice daily from 30 assumed-healthy volunteers over a 2-day period. Various statistical methods including analysis of variance (ANOVA), paired t-test and Pearson's product-moment correlation were used to evaluate the data. RESULTS: Although the basal levels of these biomarkers were varied among subjects, the data show that the concentrations of albumin, elastase and IL-8 were significantly higher in samples collected in the morning compared to samples collected later during the day. Pre-washing nasal cavity prior to collecting nasal lavage samples did alter the measurement of elastase and albumin, but did not influence the levels of the other biomarkers. CONCLUSIONS: These data show that this panel of biomarkers can be used to monitor changes in the nasal cavity including those affected by diurnal fluctuations. These results also provide useful baseline values and sources of variability for each biomarker that could be used to help design clinical trials.

A non-randomized study to investigate the effects of the atypical antipsychotic aripiprazole on the steady-state pharmacokinetics of lamotrigine in patients with bipolar I disorder.

OBJECTIVE: To determine the effect of aripiprazole on steady-state pharmacokinetics of lamotrigine in patients with bipolar I disorder who were clinically stable on lamotrigine (100-400 mg/day) for >or=4 weeks. METHODS: In this open-label study, aripiprazole was administered at 10 mg/day for 3 days, 20 mg/day for 3 days, then 30 mg/day for 8 days. Blood samples were collected on Days -1 and 14 for determination of lamotrigine steady-state pharmacokinetic parameters. Safety and tolerability were assessed. RESULTS: Eighteen patients were administered aripiprazole in combination with lamotrigine. Geometric mean (GM) values for lamotrigine maximum plasma concentration were similar for lamotrigine alone (26 ng/mL) and with co-administered aripiprazole (23 ng/mL). GM values for plasma lamotrigine area under the concentration-time curve (AUCtau) were comparable for lamotrigine alone (434 ng/h/mL) and with co-administered aripiprazole (394 ng/h/mL). Median T(max) of lamotrigine alone and combined with aripiprazole was 1.98 and 0.77 h, respectively. No changes to lamotrigine dose-normalized plasma trough concentrations were observed with co-administered aripiprazole. Sixteen patients (88.9%) experienced >or=1 adverse event (AE), the most common of which was insomnia (n = 6). CONCLUSIONS: Aripiprazole had no meaningful effect on lamotrigine steady-state pharmacokinetics in patients with bipolar I disorder. No dosage adjustment of lamotrigine is required and the combination was generally safe and well tolerated.

Effects of a preoperative femoral nerve block on pain management and rehabilitation after total knee arthroplasty.

The objective of this prospective, randomized, double-blind study was to determine if preoperative administration of a femoral nerve block reduces the amount of morphine needed for postoperative analgesia after total knee arthroplasty (TKA). Forty-two patients undergoing TKA were randomly assigned to receive either a femoral nerve block (0.50% bupivacaine hydrochloride with epinephrine 1:200,000) or matching placebo. Results showed postoperative morphine use was significantly lower in patients who received the nerve block (25.5 vs 37.5 mg, P = .016); however, the 2 groups had similar pain scores and rehabilitative outcomes. In general, a preoperative femoral nerve block is a safe and effective adjunct for decreasing morphine use for post-TKA analgesia.