Comparative study of the reactogenicity of a three-component acellular pertussis vaccine and whole-cell pertussis vaccine administered to healthy Singaporean infants.

The objective of this study was to assess and compare the reactogenicity of GlaxoSmithKline (GSK) Biologicals' diphtheria-tetanus-tricomponent acellular pertussis vaccine (DTPa) and the locally used combined diphtheria-tetanus-whole-cell pertussis vaccine (DTPw) as a primary vaccination course in healthy infants at the age of 3, 4 and 5 months. A phase IV, single-blinded, randomized comparative clinical study involved one hundred and eighty healthy infants with two study groups in a 2:1 ratio to receive either DTPa or DTPw vaccine which were administered intramuscularly at the right anterior-lateral aspect of the thigh. The incidence and intensity of local solicited symptoms such as pain, redness and swelling at injection site and general solicited symptoms such as fever and fussiness were evaluated. Serious adverse events were followed for one month after each vaccination. The overall incidence of local and general symptoms was significantly higher in the group receiving locally used DTPw vaccine as compared to the group receiving GSK DTPa vaccine. Solicited local symptoms, pain (47.4% vs 15.1%), redness (95.9% vs 84.9%) and swelling (46.2% vs 18.5%), were reported more frequently in the group receiving DTPw vaccine than in the group receiving DTPa vaccine. Fever (> or = 37.5 degrees C) (52% vs 14.6%) and fussiness (60.8% vs 33.6%) were also more commonly reported in the DTPw group. There were six serious adverse events reported (4 with DTPw and 2 with DTPa). None of them related to the study vaccines, as considered by the investigators. Thus it was found that GSK Biologicals' DTPa vaccine was significantly less reactogenic as compared to the locally used DTPw vaccine manufactured by Commonwealth Serum Laboratories when administered as a 3-dose primary vaccination course to healthy infants at the age of 3, 4 and 5 months in Singapore.

Caffeine in apnoeic Asian neonates: a sparse data analysis.

AIMS: To monitor plasma caffeine concentrations and adverse effects and to study the pharmacokinetics of caffeine in neonatal apnoea in the local Asian population after intravenous administration of caffeine. METHODS: Eighteen neonates with apnoea were treated with caffeine citrate at a loading dose of 10 mg caffeine base kg-1 and a maintenance dose of 2.5 mg kg-1 day-1. Blood samples, three after loading and two after the maintenance dose on day 2, 3, 7, 14 and 21 were taken and analysed for caffeine and its main metabolites using solid phase extraction and h.p.l.c. Adverse effects were monitored. Sparse data pharmacokinetic analysis was performed using P-Pharm. RESULTS: Mean caffeine concentrations varied from 10 to 20 mg l-1 throughout treatment (range 3.6-28.4 mg l-1). These concentrations were efficacious; less so in those with lower concentrations. Adverse effects included gastrointestinal disturbances, diuresis and hyperglycaemia. Pharmacokinetic parameter estimates [mean (coefficient of variation%)] were CL=0.00628 (17.5%) l h-1 and V=0.961 (20.3%) l. CL (l h-1)=0.004248 * wt(kg)+0.00154; r=0.8, P<0.01, explained 64% of the variation. V (l)=0.6299 * wt(kg)+0.259; r=0.67, P<0.01, explained 45% of variation. Model-predicted compared with observed plasma concentrations in a separate group of 10 neonates were unbiased and of good precision. CONCLUSIONS: The dosing regimen studied was suitable for our local Asian neonates as it resulted in therapeutic caffeine concentrations for adequate treatment of apnoea. Adverse effects were tolerable. Therefore, to avoid a higher incidence of adverse effects, this regimen should be retained and not increased as proposed by other workers. CL and V were within values of those reported for neonatal apnoea. Sparse data analysis showed that weight alone was adequate as the influential variable for the accurate prediction of individual pharmacokinetic parameters, plasma concentrations and for dosage adjustment if required.