Pediatric thioridazine poisoning as a result of a pharmacy compounding error

The adverse effects or overdose of thioridazine including sudden death, fatal arrhythmia, or retinopathy, in addition to the neurological signs have been reported. A three-year-old boy with bronchitis was prescribed erythromycin by a local clinic, but he started to complain of severe drowsiness and became unconscious. It was decided that this was a result of a compounding error of thioridazine instead of erythromycin owing to their similar commercial names. The thioridazine concentration in the child's serum on admission was two to three times higher than the Cmax for adults with the same dosage. The concentration of the lavage saline on admission was only 0.3% of the ingested amount, indicating that the lavage was not effective in our case. Pharmacokinetic analysis revealed the parameters as Tmax, 1.5 hr; Cmax, 1700 ng/mL; Ka, 2.01 L/hr; Vd, 3.6 L/kg; and T1/2, 6.8 hr. Further investigations on clinical cases with a pharmacokinetic analysis should be done to confirm the pharmacokinetic evidence obtained here and to give specific therapeutic guidelines for overdose management especially in children

Pharmacokinetics of Beclomethasone Dipropionate in an Hydrofluoroalkane-134a Propellant System in Japanese Children with Bronchial Asthma

ABSTRACTBackgroundHydrofluoroalkane-134a (HFA) has been shown to be a safe replacement for chlorofluorocarbons (CFCs) as a pharmaceutical propellant, with the advantage that it has no ozone-depleting potential. This is the first report of the pharmacokinetics of beclomethasone dipropionate (BDP) delivered from a pressurized solution formulation using an HFA propellant system (HFA-BDP) in Japanese children with bronchial asthma.MethodsPlasma concentrations of beclomethasone 17-monopropionate (17-BMP), a major metabolite of BDP, following an inhaled dose of HFA-BDP (200 μg as four inhalations from 50 μg/actuation) in five Japanese children with bronchial asthma were quantified and analyzed by a non-compartmental analysis to obtain pharmacokinetic parameters.ResultsThe area under the concentration-time curve from time zero to the last quantifiable time (AUC0-t) was 1659 ± 850 pg • h/mL (arithmetic mean ± standard deviation (SD)), the maximum concentration observed (Cmax) was 825 ± 453 pg/mL and the apparent elimination half-life (t1/2) was 2.1 ± 0.7 hours. The time to reach Cmax (Tmax) was 0.5 hours in all patients. No special relationship was observed between these parameters and age or body weight. These parameters were compared with the previously reported parameters of American children with bronchial asthma. The Japanese/American ratio of the geometric means of each parameter was 1.36 for AUC0-t, 1.04 for Cmax and 1.4 for t1/2. The median of Tmax was 0.5 hours in American patients as well as Japanese patients.ConclusionsThe pharmacokinetics of HFA-BDP in Japanese children with bronchial asthma are reported for the first time and a similarity to those in American children is suggested

Lymphocyte Responses to Chymotrypsin- or Trypsin V-Digested β-Lactoglobulin in Patients with Cow's Milk Allergy

<p/> <p>Chymotrypsin- or trypsin V- (a mixture of trypsin and chymotrypsin) digested β-lactoglobulin (BLG) peptides were prepared and were confirmed to have much less immunoglobulin (lg)G and lgE reactivity compared with intact BLG by IgG inhibition enzymelinked immunosorbent assay and IgE dot blotting. The lymphocyte responses to intact BLG and these peptides were examined using peripheral blood mononuclear cells (PBMCs) from 10 patients with cow's milk allergy. The PBMCs from most patients had lower lymphocyte responses to chymotrypsin- and trypsin V-digested BLG peptides than those to intact BLG. However, PBMCs from one and two patients retained significant proliferative responses to both peptides and to only the former peptide, respectively. Interferon-c production stimulated by chymotrypsin-digested peptides was still detectable in all five patients tested. Chymotrypsindigested BLG reduced lgE reactivity but still induced some lymphocyte responses.</p

Pediatric Reports 2009; volume 1:e9 Pediatric

thioridazine poisoning as a result of a pharmacy compounding erro

Molecular Basis of IgG2 Deficiency Molecular Basis of Selective IgG2 Deficiency The Mutated Membrane-bound Form of ␥ 2 Heavy Chain Caused Complete IgG2 Deficiency in Two Japanese Siblings

Abstract Patients with IgG2 deficiency have recurrent sinopulmonary infections caused by Pneumococcus and Hemophilus . Hereditary and selective IgG2 deficiency was suspected in two Japanese siblings whose serum IgG2 levels were under detection limits, while other serum levels of immunoglobulin subclasses were within normal ranges. Expression level of spontaneous germline C ␥ 2 transcript was normal, but that of the spontaneous mature C ␥ 2 transcript was greatly decreased in the patients&apos; PBMCs, suggesting the presence of a defect at or after the class switch to C ␥ 2. We sequenced the C ␥ 2 gene region, and in both patients a homozygous one-base insertio

Population pharmacokinetics of pranlukast hydrate dry syrup in children with bronchial asthma

Background: This is the first report about the pharmacokinetics (PK) of pranlukast in children. The aim of the present study was to assess the PK parameters of pranlukast in children and to compare them with those in adults. Methods: Six healthy adult male volunteers and 22 children with bronchial asthma at 3–14 years of age were enrolled in the study. Both 225 and 112.5 mg pranlukast hydrate dry syrup was administered orally to adults, whereas 3.5 mg/kg pranlukast hydrate dry syrup was given to children. Blood samples were obtained at approximately 20 time points per adult (n=121) and at two or three time points per child (n=54). Population PK analysis was performed using NONMEM (Globomax, Hanover, MD, USA). The concentration-time-course of pranlukast was described by using a one-compartment model with first-order absorption. The robustness of the final model was evaluated using 200 bootstrap samples. Results: Apparent clearance (CL/F) was 1.81 and 1.14 L/h per kg in children and adults, respectively. According to subgrouping of children, no significant difference was observed in CL/F between infants (3–6 years of age) and schoolchildren (7–14 years of age). The interindividual variability of CL/F accounted for 48.7%. The additive and proportional residual variability was 7.33 ng/mL and 73.8%, respectively. All fixed effect parameters fell within 10% of the bootstrapped mean. Conclusions: Compared with adults, children showed a higher CL/F and more rapid elimination after ingestion of pranlukast hydrate dry syrup. However, no significant variation was seen in CL/F between infants and schoolchildren

Questionnaire-based Study on the Relationship between Pet-keeping and Allergic Diseases in Young Children in Japan

Background: It is still unclear how early exposure to pets is related to the risk of developing atopy-related diseases in children. There are few reports on this pet-allergy relationship in Japan although much controversial data have been reported in Europe and the USA. Methods: A questionnaire on pet-keeping and allergic diseases was distributed to parents of children 3-6 years of age who belonged to 4 kindergarten and 2 nursery schools in Gifu city and surrounding areas. A total of 1185 questionnaires were analyzed statistically. Results: Bronchial asthma (11.6%), atopic dermatitis (16.5%), and allergic rhinitis (16.5%) were reported. Dogs, cats, hamsters, rabbits, and birds were kept by 21.6%, 5.5%, 10%, 1.5%, and 2.6% of all families, respectively. Indoor pets with fur resulted in a significantly higher prevalence of atopic dermatitis (OR = 1.82, 95% CI 1.26-2.63) using univariate analysis and also in multivariate logistic regression analysis. We also found a significantly higher prevalence of atopic dermatitis in subjects who started keeping dogs and/or cats indoors after 1 year of age, compared to subjects who kept neither dogs nor cats, using both univariate analysis (OR = 2.26, 95%CI 1.13-4.54) and multivariate logistic regression analysis (OR = 2.17, 95%CI 1.09-4.32). Conclusions: We found no evidence that pet-keeping protects people from developing various allergies. Conversely, indoor pets with fur have a slightly increased prevalence of atopic dermatitis