1.
Neonatal Maturation of Paracetamol (Acetaminophen) Glucuronidation, Sulfation, and Oxidation Based on a Parent-Metabolite Population Pharmacokinetic Model.
Cook, SF, Stockmann, C, Samiee-Zafarghandy, S, King, AD, Deutsch, N, Williams, EF, Wilkins, DG, Sherwin, CM, van den Anker, JN
Clinical pharmacokinetics. 2016;(11):1395-1411
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Abstract
OBJECTIVES This study aimed to model the population pharmacokinetics of intravenous paracetamol and its major metabolites in neonates and to identify influential patient characteristics, especially those affecting the formation clearance (CLformation) of oxidative pathway metabolites. METHODS Neonates with a clinical indication for intravenous analgesia received five 15-mg/kg doses of paracetamol at 12-h intervals (<28 weeks' gestation) or seven 15-mg/kg doses at 8-h intervals (≥28 weeks' gestation). Plasma and urine were sampled throughout the 72-h study period. Concentration-time data for paracetamol, paracetamol-glucuronide, paracetamol-sulfate, and the combined oxidative pathway metabolites (paracetamol-cysteine and paracetamol-N-acetylcysteine) were simultaneously modeled in NONMEM 7.2. RESULTS The model incorporated 259 plasma and 350 urine samples from 35 neonates with a mean gestational age of 33.6 weeks (standard deviation 6.6). CLformation for all metabolites increased with weight; CLformation for glucuronidation and oxidation also increased with postnatal age. At the mean weight (2.3 kg) and postnatal age (7.5 days), CLformation estimates (bootstrap 95% confidence interval; between-subject variability) were 0.049 L/h (0.038-0.062; 62 %) for glucuronidation, 0.21 L/h (0.17-0.24; 33 %) for sulfation, and 0.058 L/h (0.044-0.078; 72 %) for oxidation. Expression of individual oxidation CLformation as a fraction of total individual paracetamol clearance showed that, on average, fractional oxidation CLformation increased <15 % when plotted against weight or postnatal age. CONCLUSIONS The parent-metabolite model successfully characterized the pharmacokinetics of intravenous paracetamol and its metabolites in neonates. Maturational changes in the fraction of paracetamol undergoing oxidation were small relative to between-subject variability.
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Effect of vitamin D therapy in addition to amitriptyline on migraine attacks in pediatric patients.
Cayir, A, Turan, MI, Tan, H
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas. 2014;(4):349-54
Abstract
The purpose of this study was to investigate the effect of supplementary vitamin D therapy in addition to amitriptyline on the frequency of migraine attacks in pediatric migraine patients. Fifty-three children 8-16 years of age and diagnosed with migraine following the International Headache Society 2005 definition, which includes childhood criteria, were enrolled. Patients were classified into four groups on the basis of their 25-hydroxyvitamin D [25(OH)D] levels. Group 1 had normal 25(OH)D levels and received amitriptyline therapy alone; group 2 had normal 25(OH)D levels and received vitamin D supplementation (400 IU/day) plus amitriptyline; group 3 had mildly deficient 25(OH)D levels and received amitriptyline plus vitamin D (800 IU/day); and group 4 had severely deficient 25(OH)D levels and was given amitriptyline plus vitamin D (5000 IU/day). All groups were monitored for 6 months, and the number of migraine attacks before and during treatment was determined. Calcium, phosphorus alkaline phosphatase, parathormone, and 25(OH)D levels were also determined before and during treatment. Results were compared between the groups. Data obtained from the groups were analyzed using one-way analysis of variance. The number of pretreatment attacks in groups 1 to 4 was 7 ± 0.12, 6.8 ± 0.2, 7.3 ± 0.4, and 7.2 ± 0.3 for 6 months, respectively (all P > 0.05). The number of attacks during treatment was 3 ± 0.25, 1.76 ± 0.37 (P < 0.05), 2.14 ± 0.29 (P < 0.05), and 1.15 ± 0.15 (P < 0.05), respectively. No statistically significant differences in calcium, phosphorus, alkaline phosphatase, or parathormone levels were observed (P > 0.05). Vitamin D given in addition to anti-migraine treatment reduced the number of migraine attacks.
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A pilot study of the effects of cannabis on appetite hormones in HIV-infected adult men.
Riggs, PK, Vaida, F, Rossi, SS, Sorkin, LS, Gouaux, B, Grant, I, Ellis, RJ
Brain research. 2012;:46-52
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Abstract
RATIONALE The endocannabinoid system is under active investigation as a pharmacological target for obesity management due to its role in appetite regulation and metabolism. Exogenous cannabinoids such as tetrahydrocannabinol (THC) stimulate appetite and food intake. However, there are no controlled observations directly linking THC to changes of most of the appetite hormones. OBJECTIVES We took the opportunity afforded by a placebo-controlled trial of smoked medicinal cannabis for HIV-associated neuropathic pain to evaluate the effects of THC on the appetite hormones ghrelin, leptin and PYY, as well as on insulin. METHODS In this double-blind cross-over study, each subject was exposed to both active cannabis (THC) and placebo. RESULTS Compared to placebo, cannabis administration was associated with significant increases in plasma levels of ghrelin and leptin, and decreases in PYY, but did not significantly influence insulin levels. CONCLUSION These findings are consistent with modulation of appetite hormones mediated through endogenous cannabinoid receptors, independent of glucose metabolism.
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Pain control during fixed orthodontic appliance therapy.
Polat, O, Karaman, AI
The Angle orthodontist. 2005;(2):214-9
Abstract
The control of pain during orthodontic treatment is of great interest to both clinicians and patients. However, there has been limited research into the control of this pain, and there is no standard of care for controlling this discomfort. This prospective study determines the pain sequelae in fixed orthodontic treatment and evaluates comparatively the analgesic effects of nonsteroidal anti-inflammatory drugs for the control of this pain. One hundred and fifty orthodontic patients who were to have teeth bonded in at least one arch were randomly assigned to one of six groups: (1) placebo/placebo, (2) ibuprofen/ibuprofen, (3) flurbiprofen/flurbiprofen, (4) acetaminophen/acetaminophen, (5) naproxen sodium/naproxen sodium, and (6) aspirin/aspirin. The pain evaluations were made during chewing, biting, fitting the front teeth, and fitting the back teeth using a 100-mm visual analogue scale (VAS) for seven days. All the analgesics succeeded in decreasing the pain levels compared with the placebo group. However, naproxen sodium and aspirin groups showed the lowest pain values, and the acetaminophen group showed VAS results similar to those of the two analgesics.