ABSTRACT
Despite widespread availability of acetaminophen in Mexico, data on its pharmacokinetic properties in Mexican populations are limited. This single-center, single-blind, randomized, 2-period, 2-treatment, crossover, single-dose-per-period, 2-sequence study evaluated the bioequivalence of a test acetaminophen product available in Mexico compared with a reference 500-mg acetaminophen product in 28 healthy adults under fasting conditions. Blood samples were collected predose and at specified intervals across a 16-hour period following administration and were analyzed for acetaminophen using a validated reverse-phase high-performance liquid chromatography method. Drug products were considered to be bioequivalent if confidence intervals of natural log-transformed Cmax , AUC0-t , and AUC0-∞ data were within the range of 80% to 125%. Results were inconclusive for Cmax due to high levels of intrasubject variability with this parameter. However, criteria for bioequivalence were met for AUC0-t and AUC0-∞ . All measured acetaminophen concentrations in this study were within a safe therapeutic range, and no adverse events were reported. The level of Cmax intrasubject variability observed in this study does not have any apparent clinical implications that could affect either safety or efficacy.
Subject(s)
Acetaminophen/pharmacokinetics , Analgesics, Non-Narcotic/pharmacokinetics , Antipyretics/pharmacokinetics , Acetaminophen/administration & dosage , Acetaminophen/blood , Administration, Oral , Adult , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/blood , Antipyretics/administration & dosage , Antipyretics/blood , Cross-Over Studies , Drug Compounding , Fasting/metabolism , Female , Healthy Volunteers , Humans , Male , Middle Aged , Single-Blind Method , Therapeutic Equivalency , Young AdultABSTRACT
Gap junctional communication is mainly mediated by connexin36 and connexin43 in neurons and astrocytes, respectively. It has been suggested that connexin36 allows electrical coupling between neurons whereas connexin43 participates in several process including release of ATP. It was recently reported that blockage of gap junctional communication mediated by connexin36 can disrupt the sleep architecture of the rat. However, there is no experimental approach about effects of sleep deprivation on connexins expression. Therefore, we examined in adult male Wistar rats whether protein levels of connexin36 and connexin43 change in pons, hypothalamus, and frontal cortex after 24 h of total sleep deprivation and 4 h of sleep recovery. Western blot revealed that total sleep deprivation significantly decreases the levels of connexin36 in the hypothalamus and this decrease maintains after sleep recovery. Meanwhile, connexin43 is not altered by total sleep deprivation but interestingly the sleep recovery period induces an increase of this connexin. These results suggest that electrical coupling between hypothalamic neurons could be altered by sleep deprivation and that sleep recovery drives changes in connexin43 expression probably as a mechanism related to ATP release and energy regulation during sleep.
