慢性阻塞性肺疾病患者茶碱药动学变化及其影响因素

Pharmacokinetics of theophylline in patients with COPD and its interference factors

AIM: To study the pharmacokinetics of theophylline in patients with chronic obstructive pulmonary diseases (COPD) and its interference factors. METHODS: Serum theophylline concentrations in 9 patients with COPD after oral administration of theophylline (200 mg, tid) for 5 consecutive days or combining with nifedipine (10 mg, tid) for 5 consecutive days were determined by high performance liquid chromatography(HPLC) with ultraviolet spectrophotometry. RESULTS: The pharmacokinetics of theophylline in COPD patients was one-compartment model after oral administration of theophylline (200 mg, tid) for 5 consecutive days. The significant difference in individual variation on pharmacokinetics of theophylline was observed in this study. The volume of distribution (Vd) was (0.50±0.21) L/kg, the elimination half-life (t1/2) was (5.4±1.3) h and clearance (CL) was (0.07±0.03) L·h-1·kg-1 in the patients with COPD. There was no significant difference in Vd, t1/2, and CL between COPD patients and healthy volunteers (P>0.05). The values of k and Cl were faster and t1/2 was shorter in the middle-aged patients than those in old COPD patients (P<0.05). After administration of nifedipine for 5 consecutive days, the mean serum theophylline concentration decreased by (1.8±2.0) mg/L. The Cmax and AUC0-8 were lower than those obtained before nifedipine[(12±6) vs (10±5) mg/L, (82±52) vs (62±39) mg·L-1·h, P<0.05], respectively. In this study, the mean serum concentration of theophylline determined by UV method was significantly lower than that by HPLC [△C=(-0.6±1.6) mg/L, n=123, P<0.05]. However, the pharmacokinetic parameters of theophylline determined by the two methods were no difference(P>0.05). In addition, the results showed that there was no significant change in theophylline recovery in pure serum of theophylline and mixture serum of theophylline and CTRX. CONCLUSION: The pathological state of COPD appears not to affect the pharmacokinetic profiles in middle-aged patients with COPD. It is not necessary to change the therapeutic combination with nifedipine in COPD patients. Theophylline serum concentrations determined by HPLC and UV methods are highly correlated and both can be used in the clinical pharmacokinetics study.

AIM： To study the pharmacokinetics of theophylline in patients with chronic obstructive pulmonary diseases （COPD） and its interference factors. METHODS： Serum theophylline concentrations in 9 patients with COPD after oral administration of theophylline （200 mg, tid） for 5 consecutive days or combining with nifedipine （ 10 mg, tid） for 5 consecutive days were determined by high performance liquid chromatography（HPLC） with ultraviolet spectrophotometry. RESULTS： The pharmacokinetics of theophylline in COPD patients was one-compartment model after oral administration of theophylline （200 mg, tid） for 5 consecutive days. The significant difference in individual variation on pharmacokinetics of theophylline was observed in this study. The volume of distribution （ Vd ） was （0.50 ± 0.21） L/kg, the elimination half-life （ t1/2 ） was （5.4 ± 1.3） h and clearance （CL） was （0.07 ± 0.03） L·h^-1·kg^-1 in the patients with COPD. There was no significant difference in Vd, t1/2, and CL between COPD patients and healthy volunteers （ P 〉 0.05）. The values of k and C1 were faster and t 1/2 was shorter in the middleaged patients than those in old COPD patients （P 〈 0.05）.