695例茶碱血药浓度监测分析

目的：了解影响茶碱血药浓度的因素以指导临床用药。方法：本文对接受茶碱维持量疗法的695例患者的茶碱血药浓度监测结果进行了回顾性分析。结果：35.1%的病例茶碱血药浓度在有效血药浓度范围内（10-20μg/ml),35.8%的病例茶碱血药浓度低于10μg/ml,29.1%的病例茶碱血药浓度高于20μg/ml；环丙沙星，氟罗沙星，沙丁胺醇提高茶碱血药浓度；特布他林、利福平、速尿降低茶碱血药浓度；合并肝功能异常，肺心病患者茶碱血药浓度偏高；嗜烟患者茶碱血药浓度偏低。结论：茶碱血药浓度个体差异大，药物因素。疾病因素，嗜好等影响茶碱血药浓度，茶碱血药浓度监测对提高其使用的安全性和有效性具有重要的意义。     

非洛地平对茶碱控释片在慢性阻塞性肺疾病患者体内药动学的影响

目的观察非洛地平对茶碱控释片在慢性阻塞性肺疾病患者体内血药浓度与药动学的影响。方法采用高效液相色谱法测定合用非洛地平前后不同时间茶碱的血药浓度，采用3P87程序判别模型并计算参数。结果联用非洛地平后茶碱血药浓度比单用茶碱时消除明显减慢，但只有在给药后8.0 h合并用药比单用茶碱时茶碱血药浓度高，且差异有显著性（P＜0.05）。联用非洛地平对茶碱的消除半衰期(t1/2β)、消除速率常数(Ke)、表观分布容积（Vd）均有显著影响（均P＜0.05），AUC、Cmax、tmax、ka、t1/2α等无明显变化。结论联合使用非洛地平和茶碱时，非洛地平能延缓茶碱在慢性阻塞性肺疾病患者体内的消除，但茶碱的血药浓度能保持在正常治疗浓度范围。长期联用非洛地平和茶碱控释片需要密切监测茶碱的血药浓度。     

非洛地平对中老年慢性阻塞性肺病患者茶碱控释片药动学的影响

目的:观察钙通道拮抗剂非洛地平对茶碱血药浓度及药动学参数的影响。方法:采用荧光偏振免疫法检测8例中老年慢性阻塞性肺炎患者在联用非洛地平前后茶碱各时点的血药浓度,并用PKBP-N1程序求得药动学参数,用配对T检验法作统计学分析。结果:联用非洛地平后茶碱血药浓度比单用药时消除明显减慢,但只有在给药后8.0h一个时间点,合并用药比单用茶碱时茶碱血药浓度升高有显著性(P<0.05),而且从药动学参数来看,联用非洛地平对茶碱的消t1/2β、Ke、Vd差异有显著性。AUC、Cm ax、tm ax、Ka、t1/2α均差异无显著性(P>0.05)。结论:合用非洛地平和茶碱,非洛地平能延缓茶碱在慢阻肺患者体内的消除,茶碱的血药浓度则一直在正常治疗浓度范围,但需要密切监测茶碱的血药浓度。     

加替沙星对慢性阻塞性肺疾病患者茶碱缓释片体内清除率的影响

目的研究加替沙星对慢性阻塞性肺疾病(COPD)患者茶碱缓释片体内清除率的影响。方法通过对临床慢性COPD患者联用加替沙星前后茶碱血药浓度的测定,获得相关药动学参数并作统计处理。结果联用加替沙星前后茶碱血药浓度升高,清除率有显著降低。结论加替沙星明显延缓茶碱在体内的代谢,临床上二者联用时应监测茶碱的血药浓度,以保证安全。     

乳酸左氧氟沙星对肺心病人体内茶碱药动学的影响

应用紫外分光光度法分别测定8例肺心病患者单独静脉滴注氨茶碱及合用乳酸左氧氟沙星达稳态后茶碱的血药浓度,发现乳酸左氧氟沙星明显延长了茶碱的半衰期(P＜0.01),使茶碱达稳态时血药浓度明显升高(P＜0.01),清除率(CL)下降(P＜0.01).提示临床两药合并应用时,应加强茶碱的血药浓度监测,调整用药剂量.     

39例患者茶碱血药谷浓度监测情况分析

目的　了解我院茶碱临床使用和血药浓度监测的情况。方法　回顾分析 39例共 51例次茶碱血药谷浓度监测病例资料。结果　①茶碱血药谷浓度在 5μg/ml以上开始起效 ,不良反应主要发生于谷浓度≥ 1 5μg/ml的病例。② 51例次中 ,有 5例次 (9.8% )茶碱血药谷浓度大于 2 0 .0 μg/ml,1 6次 (31 4% )茶碱血药谷浓度小于 5 0 μg/ml。③监测的 51例次中 ,以伍用影响茶碱血药浓度药物后监测为主 (43 1 % )。换用茶碱制剂及危急情况静脉用药大多未能及时监测。④ 51例次中 ,只有 35例按监测要求进行。⑤ 51例次中剂量 -血药浓度有良好相关性的有 2 7例 ,剂量 -血药浓度相关性较差的有 8例。结论　茶碱血药浓度、药效和不良反应是有确切的内在联系 ,但茶碱个体差异较大 ,应加强茶碱的常规监测 ,确保用药安全、有效     

稳态时加替沙星对茶碱在家兔体内药动学的影响

目的 :研究稳态时加替沙星对茶碱在家兔体内药动学的影响。方法 :采用自身对照法 ,HPLC法平行监测合用药前后茶碱的血药浓度 ,通过PKBP N1软件拟合茶碱的药动学参数 ,并做统计学比较。结果 :合并用药前后茶碱的血药浓度AUC差异有显著性 (P <0 .0 5 ) ,合用后茶碱的血药浓度显著提高 ,峰时Tmax提前 ,吸收速率Ka 变大 ,消除半衰期T1 / 2 β相应延长 ,消除率相应减少。结论 :加替沙星能延缓茶碱在体内的代谢 ,提示合并用药时应对茶碱进行血药浓度监测 ,防止因茶碱代谢减慢而引起蓄积中毒。     

39例患者茶碱血药谷浓度监测情况分析

目的了解我院茶碱临床使用和血药浓度监测的情况.方法回顾分析39例共51例次茶碱血药谷浓度监测病例资料.结果①茶碱血药谷浓度在5μg/ml以上开始起效,不良反应主要发生于谷浓度≥15μg/ml的病例.②51例次中,有5例次(9.8%)茶碱血药谷浓度大于20.0μg/ml,16次(31.4%)茶碱血药谷浓度小于5.0μg/ml.③监测的51例次中,以伍用影响茶碱血药浓度药物后监测为主(43.1%).换用茶碱制剂及危急情况静脉用药大多未能及时监测.④51例次中,只有35例按监测要求进行.⑤51例次中剂量-血药浓度有良好相关性的有27例,剂量-血药浓度相关性较差的有8例.结论茶碱血药浓度、药效和不良反应是有确切的内在联系,但茶碱个体差异较大,应加强茶碱的常规监测,确保用药安全、有效.     

男性慢阻肺合并肾功能损害患者多索茶碱血药浓度影响因素分析

目的 分析男性慢性阻塞性肺疾病合并肾功能损害患者多索茶碱血药浓度监测结果,探讨多索茶碱血药浓度影响因素。方法 采用回顾性分析,收集2018年7月—2021年7月郑州市第二人民医院使用多索茶碱治疗的慢性阻塞性肺疾病合并肾功能损害的男性患者病例121例,记录血药浓度监测结果和患者人口学数据、检查指标、合并用药情况等资料。进行单因素分析,初步探讨可能的影响因素和血药浓度的关联性,并将因素纳入构建多因素线性回归模型,用以矫正混杂因素的影响。结果 单因素结果显示多索茶碱血药浓度与患者年龄(r=0.32,P<0.001),体质量(r=–0.40,P<0.001),肾小球滤过率(r=–0.24,P=0.008)的关联性存在统计学意义。相对于重度肾功能损伤的患者,轻度损伤的患者多索茶碱血药浓度更低(P=0.017),吸烟患者的多索茶碱血药浓度更低(P=0.018)。在矫正了其他因素后,结果显示年龄越大,血药浓度越高(b=0.08,P=0.032),体质量越大,血药浓度越低(b=–0.14,P<0.001),吸烟患者的血药浓度相较于不吸烟的患者更低(b=–1.30,P=0.048)。结...     

氟康唑对健康人茶碱药物动力学的影响

采用高效液相色谱法分别测定了6名健康自愿者单独静脉滴注氨茶碱及合用氟康唑后茶碱的血药浓度.结果氟康唑使茶碱的半衰期明显延长,清除率降低(P＜0.01),曲线下面积增加(P＜0.05).说明氟康唑能抑制茶碱代谢.临床两药合用时应监测茶碱血药浓度并注意调整剂量.     

Salivary theophylline monitoring in asthmatic children

The usefulness of determination of salivary concentrations of theophylline for estimation of the serum concentration of the drug was tested in asthmatic children receiving daily 15-20 mg/kg of aminophylline. Theophylline was measured in saliva samples obtained after stimulation with citric acid and bromhexine, and in the blood serum, and the ratio of saliva: serum theophylline concentrations was calculated. The correlation between saliva and serum theophylline concentration was better for saliva samples obtained after bromhexine stimulation (r = 0.9496) than after citric acid stimulation (r = 0.8506). Using the mean value of the saliva: tissue theophylline concentration ratio of 0.6795, the serum theophylline concentration may be satisfactorily predicted (r = 0.9810). The stimulation of salivation with bromhexine is more suitable for the Abbott TDX Drug Monitoring System than the stimulation with citric acid, and the method is suitable for a routine monitoring of theophylline concentrations in the course of theophylline therapy.     

Comparison between theophylline analysis by nephelometric inhibition immunoassay and high performance liquid chromatography

Rate nephelometric inhibition immunoassay (NIIA) was used to determine 94 serum theophylline concentrations, and these results were compared with those obtained using high performance liquid chromatography (HPLC) as a reference method. The measurements obtained by the nephelometric method were, on the average, 20% higher than those obtained by the chromatographic method (p less than 0.001). The coefficient of variation of the nephelometric method was 12.3%, compared with 3.9% for the chromatographic reference method. In the group of subjects having a serum concentration of caffeine greater than or equal to 0.5 microgram ml-1, the difference in serum theophylline concentration found between NIIA and HPLC correlated with serum caffeine concentration (r = 0.3755, df = 46, p less than 0.01). NIIA theophylline concentration was 8.8 +/- 3.2 micrograms ml-1 in serum from six additional patients receiving theophylline 9.1 +/- 3.4 micrograms ml-1 after adding 10 micrograms caffeine (NS), and 13.1 +/- 3.5 micrograms ml-1 after adding 10 micrograms 1,3-dimethyluric acid (p less than 0.001). We conclude that (a) the results obtained by the NIIA method are more variable and consistently higher than those obtained by the HPLC method and (b) 1,3-dimethyluric acid (a caffeine and theophylline metabolite) is responsible for this overevaluation.     

Bioavailability studies of theophylline ethylcellulose microcapsules prepared by using ethylene-vinyl acetate copolymer as a coacervation-inducing agent

The bioavailability of theophylline microcapsules prepared by using ethylene-vinyl acetate (EVA) copolymer as a coacervation-inducing agent was studied in rats. The dissolution rate of the microcapsules was determined by the rotating-basket and rotating-bottle methods. The higher the concentration of EVA copolymer used, the more sustained was the release of theophylline from the microcapsules. The mean maximum serum levels (Cmax) and time to maximum serum levels (tmax) were not significantly different for theophylline microcapsules prepared by a lower concentration of EVA copolymer (0 and 0.83%, respectively), compared with those for theophylline powder; whereas a significant difference was found when the higher concentration of EVA copolymer was used (greater than 1.7%). With regards to the area-under-the-curve (AUC) value, there was no significant difference between the theophylline powder and theophylline microcapsules. The elimination kinetics and the corresponding half-life (t1/2) were significantly different when the concentration of EVA copolymer was greater than 3.3%. From the above results, it is evident that theophylline microcapsules prepared by using 3.3 and 5.0% EVA copolymer as the coacervation-inducing agent may act as sustained-release dosage forms. The correlation between the dissolution rate in vitro and the bioavailability in rats for theophylline microcapsules was investigated. The mean Cmax and tmax correlated well with the time taken to release 75% of the drug in vitro (t 75%); however, the mean AUC showed no valid correlation with t 75%. This implies that the dissolution rate correlated better with the rate of absorption (Cmax, tmax) than with the extent of absorption (AUC).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ability of three pharmacokinetic equations to predict steady-state serum theophylline concentrations in pediatric patients.

The pharmacokinetic equations of Chiou, Koup, and Kurland are often used in the pediatric setting to predict steady-state theophylline clearance using non-steady serum theophylline concentrations. However, these equations have not been validated or compared in a pediatric population. We evaluated the ability of these equations to predict steady-state serum theophylline concentrations in 61 children (0.21-14.3 years) who received a continuous intravenous theophylline (0.79 +/- 0.12 mg/kg/h) infusion for a minimum of five half-lives. Theophylline concentrations used in the Kurland equation were obtained 10.8 +/- 4.5 h after initiation of therapy and the time between the two concentrations used in the Chiou and Koup equations was 9.2 +/- 3.9 h. Predicted steady-state theophylline concentration values for the three methods were not different from each other (p = 0.91), nor were they different from the observed steady-state concentration values (p = 0.92). The coefficient of determination for predicted vs. observed steady-state concentrations was statistically significant (p less than 0.001) and was comparable for the three methods. There was no difference in mean bias (p = 0.78), precision (p = 0.82), or % error (p = 0.86) values for the three methods. Regardless of the method used, 75 to 82% of all predicted theophylline concentrations were within 20% of the observed steady-state value. However, on average, all methods underpredicted the clearance and hence overpredicted the serum theophylline concentration. The Kurland method did not predict steady-state concentrations any better in patients who had received theophylline prior to admission.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between serum and saliva theophylline levels in patients with cystic fibrosis.

Theophylline levels in stimulated and unstimulated mixed saliva were compared with total and free (unbound) serum theophylline levels in 11 outpatients with cystic fibrosis (CF) who were using theophylline regularly. Stimulated saliva from CF patients predicted both total and unbound serum theophylline concentrations to within +/- 1 microgram/ml in 53.3 and 80.0%, respectively, of the samples examined. In addition, the total serum levels from CF patients could be used to predict unbound serum concentrations to within +/- 1 micrograms/ml in 100% of the cases examined. Furthermore, it was observed that prediction equations derived in a previous study with asthmatics employing identical methodology would allow both unbound and total serum theophylline levels to be predicted from saliva levels in CF patients with a degree of accuracy and precision that was approximately equal to or slightly better than the results obtained using prediction equations derived in other CF patients. These results indicate that saliva levels allow predictions of the unbound serum theophylline levels with greater accuracy and precision than they predict total serum theophylline levels. In addition, total serum levels can be used to reliably predict unbound serum levels. The use of mixed stimulated saliva is recommended as a reliable noninvasive method for monitoring unbound serum theophylline levels. The therapeutic range for saliva, which corresponds to the accepted total serum concentration range of 10-20 micrograms/ml, is approximately 5.55-11.3 micrograms/ml.     

Theophylline concentrations in serum, saliva, and cerebrospinal fluid in patients with essential tremor.

Theophylline concentrations in saliva and serum were compared in 20 patients with essential tremor. There was a strong correlation between the concentrations in saliva and serum (r = 0.9, slope of 0.48). The ratio between unbound and bound theophylline as assessed by ultrafiltration was 0.30. This ratio was similar to that between theophylline concentrations in CSF and serum. The theophylline concentration in serum was not predictable from that obtained in saliva in individual cases. Moreover, the levels in saliva were about 20% higher than the unbound concentrations of theophylline in serum.     

Accuracy of 11 methods for predicting theophylline dose

Eleven methods for pharmacokinetic determination of theophylline dose were compared, based on the ability of each method to predict theophylline serum concentration and clearance for adults with asthma. Predictions by each method were compared with actual serum theophylline concentrations before and after an aminophylline loading dose was administered to treat bronchospasm in 22 patients. Follow-up serum theophylline concentrations were obtained after maintenance therapy with i.v. aminophylline in 6 patients and an oral sustained-release theophylline product (Theo-Dur, Key) in 16 patients; maintenance doses administered to the patients were calculated by the method of Chiou et al. Two variations of the method of Chiou et al., seven Bayesian methods using one or more measured serum theophylline concentrations, FDA's standardized clearance estimate, and a population-based clearance-estimation method were compared. A one-compartment, open model with first-order elimination was assumed for all calculations. All 11 methods predicted steady-state concentration with minimal bias and good precision. The Chiou and Bayesian methods performed similarly, with the highest precision found for the Bayesian method that incorporated four measured concentrations. The population-based method had the highest correlation coefficient and the lowest mean error for predicting steady-state concentration. Decreasing the number of measured concentrations had a minimal effect on the various Bayesian methods. All methods evaluated are sufficiently accurate for clinical application in patients with stable, uncomplicated asthma.     

Comparison of unbound and total serum theophylline concentrations with those of stimulated and unstimulated saliva in asthmatic children

Unstimulated saliva, citric acid stimulated saliva, and serum were collected from 31 asthmatic children taking theophylline. Salivary theophylline concentrations, and total and unbound serum theophylline concentrations were measured. The correlation coefficients between both types of saliva, and total and unbound serum theophylline were all statistically significant (p less than 0.001). The highest correlation coefficients were obtained with stimulated saliva and total serum concentrations (r = 0.98), and stimulated saliva and unbound serum (r = 0.96). The coefficients when unstimulated saliva was compared to either total or unbound serum concentrations were 0.90 and 0.89, respectively. Serum binding of theophylline averaged 58.1%. Unstimulated saliva had a higher mean theophylline concentration than stimulated saliva. The results suggest that salivary monitoring using stimulated saliva may be used to predict serum concentrations with a high degree of confidence when the saliva levels are substantially lower than, higher than, or in the middle of the therapeutic range, but there is a considerable degree of uncertainty when the salivary values are near the lower or upper end of the therapeutic range.     

Comparison of the Seralyzer and EMIT systems for determination of theophylline concentrations

A reflectance photometry assay for measurement of serum theophylline concentration was evaluated by comparison with an enzyme-multiplied immunoassay technique (EMIT). The concentration of theophylline in blood samples obtained from patients receiving intravenous theophylline therapy in the pediatric intensive-care unit was measured by both the Seralyzer and the EMIT systems. The interday and intraday variability of each method were also determined by means of calibrators of known concentration (5 to 40 micrograms/mL). There was significant correlation between the serum theophylline concentrations determined by the Seralyzer system and the EMIT system. The overall standard error of the estimate was 2.3 micrograms/mL, but with operator experience this improved to 1.3 micrograms/mL. Intraday variability was 1.2 micrograms/mL for the Seralyzer and 0.7 micrograms/mL for EMIT; the respective values for interday variability were 1.4 micrograms/mL and 0.8 micrograms/mL. The Seralyzer method measures theophylline concentrations with reliability, convenience, and speed. It could be potentially useful in a satellite, clinic, or acute-care pharmacy area.     

A comparative study of the pharmacokinetics of oral preparations of theophylline

The pharmacokinetics of five preparations of theophylline--euphylline and sustained-release forms (theo-dura, retaphylline, theopac and theobilong) was studied in 50 patients with the broncho-obstructive syndrome. Blood serum theophylline concentration was determined by high performance liquid chromatography. The main differences in the pharmacokinetic parameters manifested themselves in the period of half-absorption--the least one for euphylline and the greatest one for theopac. A close correlation between blood serum theophylline concentration and the profile of theophylline release from theopac tablets was revealed. The equal theophylline concentration in blood serum was determined on the 4th and 7th days of the course treatment with sustained-release preparations administered twice a day, the concentration values ranged within the subtherapeutic level. An increase of the dose by 50-150 mg/day resulted in an increase of blood serum theophylline concentration within the therapeutic range.