Risk of nonsteroidal anti-inflammatory drug-associated renal dysfunction among neonates diagnosed with patent ductus arteriosus and treated with gentamicin.

OBJECTIVE: To evaluate the risk of nonsteroidal anti-inflammatory drug (NSAID) therapy-associated acute kidney injury (AKI) among neonates diagnosed with patent ductus arteriosus (PDA) who are treated with gentamicin. STUDY DESIGN: Multicenter retrospective observational study of patients ⩽44 postmenstrual weeks of age diagnosed with PDA who received gentamicin during hospitalization between January 2006 and December 2014. Patients with and without NSAID exposure were matched on covariates associated with AKI and NSAID therapy. The primary end point, AKI, was defined according to Kidney Disease Improving Global Outcomes neonatal criteria. RESULTS: The rate of AKI for the entire cohort (n=594) was 12% (n=71). Among neonates receiving NSAIDS, 14.8% (n=44) experienced an AKI as compared to 9.1% (n=27) for those who were not exposed (relative risk, 1.6; 95% confidence interval, 1.0 to 2.6). Therefore, the attributable risk of NSAID use was 5.7% (95% confidence interval, 0.5 to 11.0). CONCLUSION: Among neonates with PDA and receiving gentamicin, NSAID therapy increases the risk of AKI by about 6%.

Intuitive eating is associated with glycaemic control in adolescents with type I diabetes mellitus.

BACKGROUND: While there have been considerable advances in the medical management of type 1 diabetes mellitus (T1DM), for many, glycaemic control remains substandard. Nutrition and eating behaviour are important additional factors to consider with regards to T1DM management and outcomes. Intuitive eating is one such factor, and has not previously been investigated in T1DM. With this in mind, we undertook a study examining the relationship between intuitive eating and glycaemic control in adolescents with T1DM. METHODS: A case-control study of adolescents with established T1DM, and age/sex matched controls was conducted. Demographic information, the Intuitive Eating Scale (IES), and HbA1c were collected. Statistical analysis was undertaken to explore associations between the IES and HbA1c as a marker of glycaemic control. RESULTS: Data on 38 adolescents with T1DM, and 39 age/sex matched controls were obtained. Those with T1DM had significantly lower (by 0.5 SD) IES scores compared to controls (p = 0.009). Higher values of both total IES and the Eating for physical rather than emotional reasons subscale were associated with lower HbA1c: HbA1c 22% lower/whole unit increase in total IES mean score, HbA1c 11% lower/whole unit increase in Eating for physical rather than emotional reasons mean score, p = 0.017 and p = 0.009 respectively. CONCLUSION: In adolescents with T1DM, there appears to be a strong association between intuitive eating, in particular the effect of emotion on eating, and glycaemic control. In addition, those with T1DM have lower scores for their intuitive eating behaviour compared to controls. Emotional eating could be a future target for screening and potentially intervening in those with T1DM, as part of a wider treatment package to improve glycaemic control. Continuing efforts are needed to fully understand the important dynamics of diabetes, adolescence, diet, emotion, and how these factors affect long term outcomes in those with T1DM.

Family CHAOS is associated with glycaemic control in children and adolescents with type 1 diabetes mellitus.

BACKGROUND: Despite advances in the medical management of type 1 diabetes mellitus (T1DM), for many, glycaemic control remains substandard. Other factors are clearly important in determining success, or lack thereof, with diabetes management. With this in mind, we have investigated whether family CHAOS may provide a novel tool to identify when environmental confusion could impact on diabetes management and subsequent glycaemic control. METHODS: A case-control study of children and adolescents with established T1DM and age-/sex-matched controls was conducted. Demographic information, both maternal and paternal CHAOS scores, and HbA1c were collected. Statistical analysis was undertaken to explore associations between T1DM and CHAOS and between CHAOS and HbA1c. RESULTS: Data on 65 children with T1DM and 60 age-/sex-matched controls were obtained. There was no evidence of group differences for maternal CHAOS (p = 0.227), but paternal CHAOS scores were higher for the T1DM group (p = 0.041). Greater maternal and paternal CHAOS scores were both associated with higher HbA1c (p ≤ 0.027). The maternal association remained after controlling for diabetes duration, SMBG frequency, and insulin therapy. CONCLUSION: In children with T1DM, there appears to be a negative association between increased environmental confusion, as rated by CHAOS, and glycaemic control. In addition, when compared to controls, fathers of children and adolescents with T1DM appear to experience CHAOS differently to mothers. These findings contribute to the growing body of literature exploring psychosocial factors in T1DM. Continuing efforts are required to fully understand how the family and psychosocial environment interact with diabetes to impact on long-term health outcomes.

Clinical review: insulin pump-associated adverse events in adults and children.

AIMS: Insulin pumps are a vital and rapidly developing tool in the treatment of type 1 diabetes mellitus in both adults and children. Many studies have highlighted outcomes and assessed their potential advantages, but much of the data on adverse outcomes are limited and often based on outdated technology. We aimed to review and summarize the available literature on insulin pump-associated adverse events in adults and children. METHODS: A literature search was undertaken using PubMed, EMBASE, and the Cochrane library. Articles were then screened by title, followed by abstract, and full text as needed. A by-hand search of reference lists in identified papers was also utilised. All searches were limited to English language material, but no time limits were used. RESULTS: Current and past literature regarding insulin pump-associated adverse events is discussed, including potential metabolic and non-metabolic adverse events, in particular: pump malfunction; infusion set/site issues; and cutaneous problems. We show that even with modern technology, adverse events are common, occurring in over 40 % of users per year, with a minority, particularly in children, requiring hospital management. Hyperglycaemia and ketosis are now the most common consequences of adverse events and are usually associated with infusion set failure. This differs from older technology where infected infusion sites predominated. CONCLUSIONS: This timely review covers all potential insulin pump-associated adverse events, including their incidence, features, impacts, and contributory factors such as the pump user. The importance of ongoing anticipatory education and support for patients and families using this intensive insulin technology is highlighted, which if done well should improve the overall experience of pump therapy for users, and hopefully reduce the incidence and impact of severe adverse events.

Career decisions: factors that influence the Maori doctor.

BACKGROUND: Maori have known health disparities that may be addressed through increasing the cultural competency of New Zealand's medical workforce. There is a paucity of Maori health professionals choosing paediatrics or adult medicine as a career and the factors influencing their career decision are yet to be explored. AIMS: First, to differentiate factors influencing the medical career choice of non-Maori paediatricians and physicians, Maori paediatricians and physicians and other Maori doctors. Second, to identify ways in which Maori doctors may be encouraged to choose paediatricians or adult medicine. METHODS: A questionnaire was distributed by email to New Zealand physicians and paediatricians and to Maori doctors. Questions included demographic information, a matrix rating table and open-ended questions. RESULTS: Altogether 199 people accessed the questionnaire. Response rates were 9% (n = 118) for non-Maori paediatricians and physicians, 70% (n = 19) for Maori paediatricians and physicians, and 31% (n = 62) for other Maori doctors. Maori paediatricians and physicians highlighted mentoring as having significant impact on career choice. Non-Maori paediatricians and physicians regarded interest as having the most influence on career choice (P < 0.01). Lifestyle factors influenced other Maori doctors (P < 0.001). All three groups regarded poor lifestyle as having the largest negative influence. No group regarded potential income as important. CONCLUSION: Mentoring provides an opportunity to attract Maori into paediatric and adult physician training. The use of existing mentoring programmes could facilitate in expanding Maori RACP workforce development. This extended Maori workforce would have benefits for the health of New Zealand as a whole.

The utilization of poisons information resources in Australasia.

PURPOSE: To identify poisons information resources most commonly utilized by Australasian Emergency Department staff, and examine attitudes regarding the benefits and user experience of the electronic products used. METHODS: A survey tool was mailed to six Emergency Departments each in New Zealand and Australia to be answered by medical and nursing staff. RESULTS: Eighty six (71.7%) responses were received from the 120 survey forms sent: 70 (81%) responders were medical staff, the remainder nursing. Electronic resources were the most accessed poisons information resource in New Zealand; Australians preferring discussion with a colleague; Poisons Information Centers were the least utilized resource in both countries. With regard to electronic resources, further differences were recognized between countries in: ease of access, ease of use, quality of information and quantity of information, with New Zealand better in all four themes. CONCLUSIONS: New Zealand ED staff favored electronic poisons information resources while Australians preferred discussion with a colleague. That Poisons Information Centers were the least utilized resource was surprising.

Comparative safety and efficacy of two high dose regimens of oral paracetamol in healthy adults undergoing third molar surgery under local anaesthesia.

This study compared the efficacy and safety of single oral doses of 60 mg/kg and 90 mg/kg paracetamol in fit young adult patients undergoing third molar extractions. The study was a randomised, blinded, crossover design on 20 young, fit adults. Paracetamol was administered 30 minutes prior to the surgical extraction of the teeth, which was done under intravenous sedation and local anaesthesia. There were no clinically or statistically significant differences in the pain scores between 60 mg/kg or 90 mg/kg doses until the intake of rescue analgesics. There was a reduction in factor VII activity with 90 mg/kg dose compared to 60 mg/kg dose. It may be concluded that the 90 mg/kg dose, though safe, does not offer any advantages over 60 mg/kg dose of paracetamol in young fit adults undergoing third molar surgery.

Inter- and intra-rater reliability for classification of medication related events in paediatric inpatients.

BACKGROUND: In medication safety research studies medication related events are often classified by type, seriousness, and degree of preventability, but there is currently no universally reliable "gold standard" approach. The reliability (reproducibility) of this process is important as the targeting of prevention strategies is often based on specific categories of event. The aim of this study was to determine the reliability of reviewer judgements regarding classification of paediatric inpatient medication related events. METHODS: Three health professionals independently reviewed suspected medication related events and classified them by type (adverse drug event (ADE), potential ADE, medication error, rule violation, or other event). ADEs and potential ADEs were then rated according to seriousness of patient injury using a seven point scale and preventability using a decision algorithm and a six point scale. Inter- and intra-rater reliabilities were calculated using the kappa (kappa) statistic. RESULTS: Agreement between all three reviewers regarding event type ranged from "slight" for potential ADEs (kappa = 0.20, 95% CI 0.00 to 0.40) to "substantial" agreement for the presence of an ADE (kappa = 0.73, 95% CI 0.69 to 0.77). Agreement ranged from "slight" (kappa = 0.06, 95% CI 0.02 to 0.10) to "fair" (kappa = 0.34, 95% CI 0.30 to 0.38) for seriousness classifications but, by collapsing the seven categories into serious versus not serious, "moderate" agreement was found (kappa = 0.50, 95% CI 0.46 to 0.54). For preventability decision, overall agreement was "fair" (kappa = 0.37, 95% CI 0.33 to 0.41) but "moderate" for not preventable events (kappa = 0.47, 95% CI 0.43 to 0.51). CONCLUSION: Trained reviewers can reliably assess paediatric inpatient medication related events for the presence of an ADE and for its seriousness. Assessments of preventability appeared to be a more difficult judgement in children and approaches that improve reliability would be useful.

The effect of sepsis upon gentamicin pharmacokinetics in neonates.

AIM: To investigate the effect of sepsis upon the volume of distribution (Vd) of gentamicin in neonates. METHODS: A retrospective chart review was conducted of neonates admitted to Dunedin Hospital who had gentamicin concentrations performed between 1st January 2000 and 30th October 2003. Data from 277 neonates, including a total of 576 gentamicin concentrations, were included in the pharmacokinetic analysis. Fifteen (5.4%) of the neonates had confirmed sepsis. Pharmacokinetic analyses were performed with NONMEM using a one compartment first order elimination model. Duration of infusion (D) was included as a parameter in the model. Covariates included sepsis (SEP), chronological age, gestational age (GA), birth weight, current weight, gender, Apgar score at 1 (AP1) and 5 (AP2) minutes, plasma C-reactive protein and serum creatinine. RESULTS: The initial model provided a mean estimates of clearance (CL) of 0.0460 l kg(-1) h(-1), volume of distribution (Vd) of 0.483 l kg(-1) and D of 0.748 h. The magnitudes of interpatient variability, expressed as CV%, were 29.2% for CL, 20.8% for Vd and 71.5% for D. The magnitude of residual variability in gentamicin concentrations was 88.0%. The final pharmacokinetic model was: CL = (0.0177 + 0.00147.(GA-20) + 0.000635.AP2) l kg(-1) h(-1), Vd = (0.483 +0.0656. sepsis) l kg(-1), D = 0.672 h. The interpatient variability (CV%) was 22.8% for CL, 22.8% for Vd and 97.7% for D. The magnitude of residual variability in gentamicin concentrations was 83.3%. CONCLUSIONS: The 14% increase in Vd in septic neonates implies that larger doses may be required to achieve peak therapeutic concentrations in the presence of sepsis. D is an important parameter in neonatal pharmacokinetic models.

Infant pertussis deaths and the management of cardiovascular compromise.

Infants infected with Bordetella pertussis in the first few weeks of life are at risk of death from 'overwhelming cardiovascular compromise despite intensive care support'. The mechanisms of this severe disease are not completely understood. Three case histories, including that of one infant who survived, are presented. Two of the patients died despite intensive therapy with pressors and, in one child, milrinone. The third child survived following treatment with nitric oxide and sildenafil. Hence, sildenafil in combination with nitric oxide shows promise as a therapy for the haemodynamic consequences of pertussis toxaemia and this should prompt clinical trials for their efficacy for this condition.

Serious lead poisoning in childhood: still a problem after a century.

OBJECTIVE: To describe a series of patients with clinically significant lead poisoning. METHODOLOGY: A case series of nine patients with lead poisoning who required inpatient management, identified through a Clinical Toxicology Service. RESULTS: Nine children presented with clinically significant lead poisoning. The median serum lead was 2.5 micro mol/L (range 1.38-4.83). Eight of the children were exposed to lead-based paint, with seven due to dust from sanded lead paint during house renovations. Serial blood determinations suggested re-exposure in four of the patients, and in one of these patients the re-exposure was from a different source of lead. Eight of the patients required chelation therapy. CONCLUSIONS: Serious lead poisoning continues to occur and there appears to be complacency regarding the hazard posed by lead paint in old houses.

Tolerability of topiramate in children and adolescents.

OBJECTIVE: To examine the tolerability of topiramate (TPM) in paediatric practice. METHODOLOGY: A retrospective cohort study of patients aged less than 18 years commenced on TPM by paediatric neurologists. Patients were identified from the dispensing databases of two paediatric tertiary referral hospitals and from the authority prescription records of four paediatric neurologists. The clinical data were obtained from the patients' medical records. RESULTS: There were 159 patients who were identified as having been commenced on TPM and follow-up data were available for 127 (80%) patients. The median (range) age at commencement of TPM was 8.1 (0.5-17.9) years, with 12 patients aged less than 2 years. After 4 years, 60% of patients had ceased the medication. Treatment limiting adverse effects included aggression/psychosis (n = 10), cognitive impairment/sedation (n = 6), anorexia/weight loss (n = 4) and desquamation (n = 1). Prior aggression (hazard ratio 5.91 (2.12-16.44)) and female gender (hazard ratio 2.94 (1.02-8.41)) were risk factors for ceasing TPM because of an adverse event. Thirty percent of children commenced on TPM experienced a treatment limiting adverse effect within 2 years of commencement. CONCLUSIONS: The frequency of treatment limiting adverse events in children receiving topiramate is higher than previously reported.

Acetazolamide poisoning in a toddler.

Acetazolamide ingestion and its sequelae have not been previously reported in children. A 12-month-old girl, weighing 10 kg, developed metabolic acidosis following ingestion of between 500 and 1250 mg of acetazolamide. The maximum base deficit recorded was 11.6. She was treated with sodium bicarbonate and recovered completely. Accidental poisoning should be included in the differential diagnosis of a child presenting with metabolic acidosis.

Valproic acid has temporal variability in urinary clearance of metabolites.

The reasons for the intra- and interindividual variability in the clearance of valproic acid (VPA) have not been completely characterized. The aim of this study was to examine day-night changes in the clearance of 3-oxovalproate (3-oxo-VPA), 4-hydroxy-valproate (4-OH-VPA), and valproic acid glucuronides under steady state. Six diurnally active healthy male volunteers ingested 200 mg sodium valproate 12 hourly, at 0800 and 2000, for 28 days. On the last study day, two sequential 12-h urine samples were collected commencing at 2000 the evening before. Plasma samples were obtained at the end of each collection. Following alkaline hydrolysis, urine was analyzed for concentrations of VPA, 3-oxo-VPA, and 4-OH-VPA. A separate aliquot was assayed for creatinine (CR). The plasma concentrations of VPA, 3-oxo-VPA, 2-en-VPA, and CR were determined. The analysis of VPA and its metabolites was performed by GC-MS. There was an increase in plasma 3-oxo-VPA concentration at 0800, sampling as compared to 2000 sampling (p < .05). The urinary excretion of 3-oxo-VPA and VPA glucuronides were decreased between 2000 and 0800, compared to between 0800, and 2000, by 40% and 50% respectively (p < .05). These results indicate a nocturnal decrease in renal clearance of 3-oxo-VPA rather than a decrease in the beta-oxidation of VPA at night. These differences were not explained by differences between the sampling periods in CR excretion. These results indicate the importance of collecting samples of 24-h duration when studying metabolic profiles of VPA.

Population pharmacokinetic modeling of steady state carbamazepine clearance in children, adolescents, and adults.

Carbamazepine (CBZ) clearance decreases from childhood to adulthood and the factors determining this change could include age, size, autoinduction, or maturational changes. This study aims to describe the population pharmacokinetics of CBZ in children and young adults and test the hypothesis that CBZ clearance correlates with weight, surface area, and age. CBZ therapeutic drug monitoring data (sparse data) were collected from child and adult epileptics, and rich data were obtained from a bioequivalence study of CBZ in young adults. Population pharmaco-kinetic analysis was performed using NONMEM V. Forward stepwise, multiple regression was performed on the covariates. Bootstrap validation was performed. A total of 946 observations from 91 subjects, ages 0.7-37 years, were collected and analyzed. A one-compartment, first-order absorption and elimination model, with exponential interindividual error and additive residual error models was developed. The population model was: Clearance (Lhr-1) = ((2.24 x Surface area (m2)) + (0.047 x Dose (mg.kg-1)); Volume of distribution (L) = 0.37 x weight (kg); Absorption rate constant = 0.013 (hr-1). CBZ clearance increased with surface area and dose.

Childhood poisoning in Queensland: an analysis of presentation and admission rates.

OBJECTIVE: To determine the presentation rates for paediatric poisoning by ingestion and the determinants of hospital admission. METHODOLOGY: Cross-sectional survey using an injury surveillance database from emergency departments in South Brisbane, Mackay and Mt Isa, Queensland, from January 1998 to December 1999. There were 1516 children aged 0-14 years who presented following ingestional poisoning. RESULTS: The presentation rates for poisoning were 690, 40 and 67 per 100000 population aged 0-4, 5-9 and 10-14 years, respectively. The admission rates to hospital for poisoning were 144, 14 and 22 per 100000 population aged 0-4, 5-9 and 10-14 years, respectively. Although presentation rates for poisoning were higher in the rural centres the admission rates were disproportionately high for the 0-4 years age group. The agents most frequently ingested were paracetamol, Dimetapp, rodenticides and essential oils. CONCLUSION: There is a need to design and implement interventions aimed at reducing poison exposures and unnecessary hospital admissions in the 0-4 years age group.

Acetaminophen causes an increased International Normalized Ratio by reducing functional factor VII.

Acetaminophen may increase International Normalized Ratio (INR) in patients taking anticoagulation medication, and in patients with acetaminophen poisoning without hepatic injury. The objective of this study was to describe and investigate the effect of acetaminophen on INR. The authors studied patients admitted to a regional toxicology treatment center with acetaminophen poisoning with INR and without potentially confounding coingestion or hepatic injury. Exposed and nonexposed (control) cohorts were recruited from admissions with acetaminophen poisoning and psychotropic drug poisoning, respectively. From 1,437 acetaminophen poisonings, after exclusions, there were 143 admissions with 205 estimations of INR. INR showed a time-dependent increase. Fifty percent of all patients and 66% of those with an extrapolated 4-hour acetaminophen concentration > or = 150 mg/L had an abnormal INR at some time. Dose ingested (p = 0.01) and nomogram-based risk (p for trend = 0.005) were correlated with the effect. N-acetylcysteine had a protective effect. Functional factor VII was lower (p = 0.005) in exposed patients (n = 30) than controls (n = 8), and less than antigenic factor VII in exposed patients (p = 0.03). Factor IX was lower (p = 0.02). Factor VIIIc was not significantly different. The authors concluded that an isolated, small rise in INR is common after acetaminophen poisoning without hepatic injury. It appears to be caused by inhibition of Vitamin K-dependent activation of coagulation factors. This effect suggests a possible mechanism for the observed interaction between acetaminophen and warfarin.

The effect of body size on the metabolic clearance of carbamazepine.

OBJECTIVES: To examine the profile of the known pathways of carbamazepine (CBZ) metabolism in a group of children and adolescents, and to test for associations with physical measurements, age and plasma hormonal levels. STUDY DESIGN: Cross-sectional study of children and adolescents attending a neurological outpatients department who were medicated with CBZ. Partial clearances of CBZ to CBZ-epoxide (CBZ-ep), CBZ-10,11-trans-diol (CBZ-diol), 2-hydroxy-CBZ (CBZ-2-OH), 3-hydroxy-CBZ (CBZ-3-OH), CBZ-acridan (CBZ-acr) and their respective glucuronides were calculated by relating 24-h recovery of these metabolites from urine to trough steady-state serum CBZ levels. CBZ and its metabolites were measured by a gradient high performance liquid chromatography (HPLC) method. Serum CBZ-ep, LH, FSH, prolactin, IGF-I, and testosterone or oestradiol and progesterone were also measured. Surface area (SA) and liver volume (LV) were calculated from height and weight. RESULTS: Twelve males and nine females with an age range of 6-17 years participated in the study. Partial clearance to each of the metabolites was most strongly correlated with the calculated size of the liver relative to body weight. These associations persisted when corrected for potential confounders using multiple regression analysis. CONCLUSION: In the age group studied, urinary clearance of CBZ to its known metabolites is proportional to the size of the liver relative to body weight.

Are metalloproteins and acute phase reactants associated with cardiovascular disease in end-stage renal failure?

End-stage renal failure (ESRF) is associated with a higher risk of cardiovascular disease (CVD) than predicted by the major risk factors. We investigate the hypothesis that metalloproteins such as transferrin and ceruloplasmin and the inflammatory response are associated with CVD risk in this population. In this cross-sectional study of 81 subjects stable on haemodialysis (HD), 43 with CVD and/or peripheral vascular disease (PAD) were compared to 38 subjects without clinical evidence of CVD/PAD. Serum concentrations of metalloproteins and acute phase reactants were compared by univariate analysis and logistic regression modelling. Body mass index, gender ratios, prevalence of diabetes, iron status, and homocysteine concentrations did not differ significantly between the groups. Those with CVD were older (P< 0.001) and had been on dialysis for longer (P = 0.004). CVD subjects had significantly higher concentrations of ceruloplasmin (325 vs 284 mg/L, P = 0.011), copper (18.2 vs 15.7 micromol/L, P = 0.002), and C-reactive protein (CRP) (median 9.0 vs 3.8 mg/L, P = 0.002). Transferrin iron binding capacity tended to be higher in the CVD group (P = 0.088). CVD risk for subjects with serum concentrations in the upper tertile was increased 9.4-fold (CI 2.8-31.0) for copper, 4.2-fold (CI 1.5-12.2) for ceruloplasmin, 3.9-fold (CI 1.3-12.1) for transferrin iron binding capacity, and 2.3-fold (CI 0.9-6.1) for CRP. In multivariate logistic regression models, age (P = 0.001) and time on dialysis (P = 0.002) were the strongest risk factors for CVD. After adjustment for age and time on dialysis, transferrin iron binding capacity (P = 0.013) and copper (P = 0.019) continued to be associated with CVD risk but ceruloplasmin (P = 0.065) and CRP (P = 0.634) were not. Total cholesterol was associated with a lower risk of CVD (ie protective), presumably due to cholesterol-lowering therapy in high-risk patients. In conclusion, copper and transferrin iron binding capacity may be associated with CVD risk in HD subjects.

Urinary excretion of valproate metabolites in children and adolescents.

The objective of this communication is to describe the changes in the metabolic profile of valproic acid (VPA) from early to late childhood and adolescence. A cross-sectional study of 12 children and adolescents attending a neurological outpatients department, who were medicated with VPA, was carried out. The proportions of daily dose excreted as VPA-glucuronide, 3-oxo-VPA and 4-OH-VPA were calculated by relating 24-h recovery of these metabolites from urine to daily VPA dose. VPA, 3-oxo-VPA and 2-en-valproic acid (2-en-VPA) were measured in trough serum samples. VPA and its metabolites were measured using a capillary gas chromatograpy method. The proportion of daily dose recovered as VPA-glucuronide in children 10 years and younger was smaller than in older children (p<0.05). There were no differences between age groups in the recovery of the other measured metabolites. Lamotrigine (LTG) comedication was also associated with a higher proportion of VPA dose recovered as glucuronide (p<0.01). LTG comedication had a stronger association with a higher proportion of dose being recovered as VPA-glucuronide on multivariate analysis than did the age group (p=0.001 versus p<0.05). In conclusion, older children and adolescents, when compared with younger children, and those comedicated with LTG excrete a higher proportion of VPA dose as VPA-glucuronide.