Clin Pharmacokinet
-
Randomized Controlled Trial Clinical Trial
The effect of dosing frequency on the pharmacokinetics of a fentanyl HCl patient-controlled transdermal system (PCTS).
The fentanyl HCl patient-controlled transdermal system (PCTS) is a noninvasive, needle-free, credit card-sized drug delivery system designed for the on-demand management of acute pain in a medically supervised setting. The objective of these studies was to determine the effect of dosing frequency on the pharmacokinetics of fentanyl delivered by the PCTS. ⋯ The amount of fentanyl absorbed from the PCTS increases as a function of time and is independent of both dosing frequency and total number of doses delivered. The fentanyl HCl PCTS is generally safe and well tolerated.
-
Randomized Controlled Trial Clinical Trial
Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol.
Gefitinib (IRESSA, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, has been approved in several countries for the treatment of advanced non-small-cell lung cancer. Preclinical studies were conducted to determine the cytochrome P450 (CYP) isoenzymes involved in the metabolism of gefitinib and to evaluate the potential of gefitinib to cause drug interactions through inhibition of CYP isoenzymes. Based on these findings, three clinical studies were carried out to investigate pharmacokinetic drug interactions in vivo with gefitinib. ⋯ Although CYP3A4 inducers may reduce exposure to gefitinib, further work is required to define any resultant effect on the efficacy of gefitinib. Exposure to gefitinib is increased by coadministration with CYP3A4 inhibitors, but since gefitinib is known to have a good tolerability profile, a dosage reduction is not recommended. Gefitinib is unlikely to exert a clinically relevant effect on the pharmacokinetics of drugs that are dependent on CYP2D6-mediated metabolism for their clearance, but the potential to increase plasma concentrations should be considered if gefitinib is coadministered with CYP2D6 substrates that have a narrow therapeutic index or are individually dose titrated.
-
Randomized Controlled Trial
Pharmacokinetics and dose proportionality of fentanyl effervescent buccal tablets in healthy volunteers.
Fentanyl effervescent buccal tablets (FEBT) are designed to enhance the rate and efficiency of fentanyl absorption through the buccal mucosa. This study was undertaken to characterise the pharmacokinetics and assess the dose proportionality of FEBT in healthy volunteers within the potential therapeutic dose range. ⋯ The pharmacokinetics of FEBT were characterised by a high early fentanyl concentration as a result of absorption across the buccal mucosa of the oral cavity, which results in bypassing first-pass metabolism. This high early tmax contributed to enhanced early systemic fentanyl exposure. Maximum concentration and AUCinfinity of FEBT increased in a dose-proportional manner from 200 to 810microg. This study provides preliminary pharmacokinetic data for FEBT across the potential therapeutic dose range.
-
Inadequate pain control in the postoperative period not only contributes to patient discomfort, but also causes physiological changes that may result in increased risk of myocardial ischaemia, deep vein thrombosis and pulmonary embolism. These events complicate postoperative recovery and may lead to longer hospital stays as well as increased healthcare costs. Patient-controlled analgesia (PCA) has emerged as an effective way for patients to manage their pain, allowing self-administration of small doses of analgesics to maintain a certain level of pain control. ⋯ The on-demand dosing and pharmacokinetics of this system differentiate it from the passive transdermal formulation of fentanyl designed for the management of chronic pain. Clinical studies have shown that the fentanyl HCl PCTS is effective in the management of acute postoperative pain. These studies have also demonstrated that the system is safe and well tolerated by patients.
-
Randomized Controlled Trial
Effects of enteral feeding on the oral bioavailability of moxifloxacin in healthy volunteers.
Moxifloxacin is a new generation fluoroquinolone antimicrobial agent used worldwide. In clinical practice in intensive care units, moxifloxacin may be frequently administered through a nasogastric feeding tube. In the absence of an oral liquid formulation and since the multivalent cations contained in enteral feeds may potentially impair absorption of moxifloxacin administered via this route, we studied the effect of concomitant enteral feeding on the pharmacokinetics and tolerability of moxifloxacin administered as a crushed tablet through the nasogastric tube. ⋯ There was no clinically relevant effect of enteral feeding on the pharmacokinetics of oral moxifloxacin in healthy volunteers. This result has to be evaluated in patients, particularly those from the intensive care unit, who are characterised by severe infectious and/or concomitant diseases that might influence absorption of moxifloxacin.