Comparative study of the pharmacokinetic characteristics of slow release theophylline oral preparations in Thai children with persistent asthma.

Significant differences in the rate and extent of absorption exist between slow release theophylline (SRT) preparations. The pharmacokinetic characteristics of Xanthium were compared with those of Theo-Dur in twelve Thai children with stable persistent asthma by randomized, double blind, crossover study. Serum theophylline concentrations (STCs) were determined by fluorescence polarization immunoassay. The pharmacokinetic parameters were estimated by using a computer program (Topfit 2.0). The STCs, at steady state after different doses, were predicted by using the modified Wagner-Nelson Equation. The mean resident time (MRT) and apparent T1/2 were significantly larger for Xanthium, but the Cmax and AUC0-infinity of Xanthium were significantly lower than those of Theo-Dur. The Frel of Xanthium was 80.1% relative to Theo-Dur. The appropriate dosing interval of both preparations for Thai children was twice a day.

Gentamicin pharmacokinetics in Thai neonates: recommendation for a dosing guideline.

A pharmacokinetic study of gentamicin was performed on 32 Thai neonates. After a single intravenous infusion of gentamicin at 2.5 mg/kg body weight, blood samples were collected at 0.5 and 12 hours. Serum gentamicin concentrations were determined with use of fluorescence polarizing immunoassay. None of the neonates with < 28 weeks post conceptional age (PCA), contrary to most of the more mature neonates, achieved the recommended therapeutic peak concentrations. The volume of distribution (Vd) and elimination half-life (T1/2) of gentamicin were found to reversely correlate with the PCA, with significantly larger Vd and longer T1/2 values observed among the premature neonates. Our findings were similar the results previously reported in Caucasians, and thus strongly indicated the necessity of gentamicin dosage adjustment among Thai neonates according to their PCA. A gentamicin dosing guideline for Thai neonates has been proposed, nonetheless, with higher doses and longer dosing intervals recommended among premature neonates.

Evaluation of threshold criteria for the nasal histamine challenge test in perennial allergic rhinitis.

Nasal reactivity to histamine was determined in patients with perennial allergic rhinitis and in control subjects. A histamine titration method delivered by a metered dose pump was used. Stuffiness, itching, and the number of sneezes were recorded, nasal secretions measured, and nasal airway resistance was recorded by active anterior rhinomanometry. Increased nasal reactivity to histamine was observed among rhinitic patients and inversely correlated with the severity of nasal symptoms. A 3-fold increase of post-saline nasal airway resistance (NAR) best differentiated the nasal responses to histamine in rhinitic patients from those in control subjects. A histamine dose of < or = 2.5 microg provoked a 3-fold increase in NAR, strongly suggesting moderate or severe symptomatic rhinitis in most cases. Nasal provocation techniques might be a useful tool for objectively assessing disease severity and response to treatment in perennial allergic rhinitis.

A single-dose comparison of three slow-release theophylline oral preparations in healthy Thai volunteers.

The study was done to compare the pharmacokinetic characteristics of three slow-release theophylline (SRT) preparations. Twelve healthy nonsmokers were randomly assigned a single dose of the following treatments at weekly intervals: Theo-Dur, Theo-24 or Xanthium orally, or aminophylline intravenously. Serially collected serum samples were analyzed for theophylline with use of fluorescence polarization immunoassay (FPIA). All three SRT preparations showed reliable absorption characteristics, but Theo-Dur had a shorter Tmax and MRT and a higher Ka. The pharmacokinetic characteristics of Theo-24 and Xanthium were similar except that Xanthium had lower bioavailability. Using single dose data for simulation of steady state pharmacokinetics, we found that a once-a-day dosage regimen with either Theo-24 or Xanthium would maintain serum levels within the therapeutic range for average non-smoking young adults whereas more frequent dosing intervals with Theo-Dur would be more appropriate. Our results argue against open substitution of SRT preparations without, close monitoring of the serum theophylline concentrations when a change is made.