Therapeutic drug monitoring
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Carboplatin (CBDCA) is a widely used anticancer agent for which dose-effect and dose-toxicity relationships have been demonstrated, thus stressing the need for a controlled exposure to this drug. So far, carboplatin administration could only be individualized a priori following 2 classic methods, which are based on the evaluation of renal clearance: Calvert's and Chatelut's formulas. This study was designed to develop and evaluate the performance of an alternative CBDCA 120-hour schedule coupled to a Bayesian adaptive dosing with feedback strategy. ⋯ Despite the markedly higher doses administered, no severe toxicities were reported in the patients treated following this new schedule. It is noteworthy that neither hematologic growth factors nor stem cells, usually associated with high-dose regimen, were used as support in this study. These data strongly suggest that it is possible to deliver higher dose- intensities of carboplatin, even in elderly, unselected patients, without increasing toxicities and with no growth factor support, provided that a therapeutic drug monitoring strategy with real-time tailored dosing is performed.
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Randomized Controlled Trial
Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract.
Cannabidiol (CBD) is known to modify the effects of Delta-tetrahydrocannabinol (THC) by decreasing anxiety and antagonizing other THC-effects. As a reason, pharmacodynamic as well as pharmacokinetic mechanisms were suggested. In context of the use of cannabis-based medicine extracts for therapeutic purposes, a study was performed in a double-blind and placebo-controlled cross-over design in which each of 24 volunteers (12 male and 12 female, age 18-45 years) obtained soft-gelatin capsules with 10 mg THC (THC-set), cannabis extract containing 10 mg THC +5.4 mg CBD (CAN-set) or placebo in weekly intervals. ⋯ However, the effect of CBD is small in comparison to the variability caused by other factors. Therefore, a pharmacokinetic reason for the differences determined between pure THC and cannabis extract is improbable at the doses chosen in this study. Significantly higher AUC and Cmax and shorter tmax were found for females as compared with males.
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Case Reports
Hepatocellular damage following therapeutic intravenous iron sucrose infusion in a child.
The maximum tolerated single dose of intravenous iron infusion and iron pharmacokinetics are not known in children and not clear in adults. The case reported here is of a child given a large dose of intravenous iron sucrose (16 mg/kg) over 3 hours, who subsequently developed features of systemic iron toxicity. A TDM consultant discusses the case in the context of toxicokinetic analysis. Because the maximum tolerated dose and pharmacokinetics of intravenous iron preparations are not known, their use in both adults and children should still be undertaken with caution.
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Comparative Study Clinical Trial
Inter- and intraindividual variabilities in pharmacokinetics of fentanyl after repeated 72-hour transdermal applications in cancer pain patients.
Perception of pain by the patient is frequently one of the early signs preceding a diagnosis of cancer and, later, a sinister sign of disease progression. Among opioid drugs, transdermal fentanyl has been evaluated in the treatment of moderate to severe cancer pain. The objective of this study was to investigate the intra- and interindividual variabilities in pharmacokinetics after fentanyl drug delivery by the transdermal fentanyl patch delivery system in patients with cancer pain. ⋯ From 25 to 100 mug/h fentanyl delivery rate, the pharmacokinetics was linear. At the 2 highest doses, an increase of total clearance was observed (>60 L/h). For the whole group, transdermal fentanyl treatment provided good to excellent pain relief in the majority of patients.
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Comparative Study
A multidisciplinary approach to the toxicologic problems associated with the use of herbal medicines.
In Hong Kong, a multidisciplinary team consisting of a pharmacist, a chemical pathologist, a scientific officer, and a physician has jointly provided an advisory service on herbal safety to healthcare professionals of all public hospitals since August 2000. This paper reports the first 2 years of experience of this team to emphasize the importance of a multidisciplinary approach to herbal poisoning. Twenty referrals received from the public hospitals from August 2000 to June 2002 were reviewed. ⋯ The 4 patients with acute renal failure and tetrahydropalmatine poisoning received these toxic herbs, which were not listed in the prescriptions, as a result of poor dispensing practice or for other reasons. Toxicological problems associated with the use of herbal medicines are complex and may be easily overlooked. A multidisciplinary team of experts should be made available to provide advice to frontline healthcare professionals.