[Show abstract][Hide abstract] ABSTRACT: To investigate glutathione and antioxidant status changes in erythrocytes from febrile children receiving repeated supratherapeutic paracetamol doses.
Fifty-one children aged 2 months to 10 years participated in the study. Three groups were studied: group 1 (n = 24) included afebrile children who did not receive paracetamol; and groups 2 (n = 13) and 3 (n = 14) included children who had fever above 38.5 degrees C for more than 72 h. Patients in group 2 received paracetamol at a dose of 50 +/- 15 (30-75) mg kg(-1) day(-1) and those in group 3 received paracetamol above the recommended therapeutic dose, ie 107 28 (80-180) mg kg(-1) day(-1). A blood sample was taken for the measurement of liver transaminases, gammaglutamil transferase (GGT), reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), superoxide dismutase (SOD) and antioxidant status.
Aspartate aminotransferase activity in group 3 was higher than in the other groups (P = 0.027). GSH, SOD and antioxidant status were significantly lower in group 3 compared with groups 1 and 2 (mean differences: for GSH 3.41 micromol gHb(-1), 95% confidence interval (CI) 2.10-4.72, and 2.15 micromol gHb(-1), 95% CI 0.65-3.65, respectively; for SOD 856 U min(-1) gHb(-1), 95% CI 397-1316, and 556 U min(-1) gHb(-1), 95% CI 30-1082, respectively; and for antioxidant status 0.83 mmol l(-1) plasma, 95% CI 0.30-1.36, and 0.63 mmol l(-1) plasma, 95% CI 0.02-1.24, respectively). GR activity was significantly lower in groups 3 and 2 in comparison with group 1 (mean differences 3.44 U min(-1) gHb(-1), 95% CI 0.63-6.25, and 5.64 U min(-1) gHb(-1), 95% CI 2.90-8.38, respectively). Using multiple regression analysis, paracetamol dose was found to be the only independent variable affecting GR, GST and SOD activities (P = 0.007, 0.003 and 0.008, respectively).
In febrile children, treatment with repeated supratherapeutic doses of paracetamol is associated with reduced antioxidant status and erythrocyte glutathione concentrations. These significant changes may indicate an increased risk for hepatotoxicity and liver damage.
British Journal of Clinical Pharmacology 04/2003; 55(3):234-40. DOI:10.1046/j.1365-2125.2003.01723.x · 3.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: During lactation, multiple situations can arise that require maternal pharmacological treatment. Because of the many health advantages of human milk to infants, breast feeding should be interrupted only when the needed drug might be harmful to the nursing child and exposure via the breast milk will be sufficient to pose a risk. Since the majority of drugs have not been shown to cause adverse effects when used during lactation, and even temporary interruption of breast feeding can be difficult for the nursing dyad, decisions regarding maternal medication use during breast feeding should be based on accurate and up-to-date information. This article reviews available data on the most commonly used antibiotics and analgesics. The use of most antibiotics is considered compatible with breast feeding. Penicillins, aminopenicillins, clavulanic acid, cephalosporins, macrolides and metronidazole at dosages at the low end of the recommended dosage range are considered appropriate for use for lactating women. Fluoroquinolones should not be administered as first-line treatment, but if they are indicated, breast feeding should not be interrupted because the risk of adverse effects is low and the risks are justified. Paracetamol (acetaminophen), low-dose aspirin (acetylsalicylic acid) [up to 100 mg/day] and short-term treatment with NSAIDs, codeine, morphine and propoxyphene are considered compatible with breast feeding. Safer alternatives should be considered instead of dipyrone, aspirin at a dosage >100 mg/day and pethidine (meperidine). In the light of the many safe alternatives for pain control, breast-feeding mothers should not be allowed to experience pain or be made to feel that they must choose between analgesia and breast feeding.
Drug Safety 01/2003; 26(13):925-35. DOI:10.2165/00002018-200326130-00002 · 2.82 Impact Factor