Ciprofloxacin Pharmacokinetics After Oral and Intravenous Administration in (Morbidly) Obese and Non-obese Individuals: A Prospective Clinical Study,Clinical Pharmacokinetics

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Ciprofloxacin Pharmacokinetics After Oral and Intravenous Administration in (Morbidly) Obese and Non-obese Individuals: A Prospective Clinical Study
Clinical Pharmacokinetics ( IF 4.6 ) Pub Date : 2022-06-01 , DOI: 10.1007/s40262-022-01130-5
Koen P van Rhee ₁ , Cornelis Smit ₂ , Roeland E Wasmann ₃ , Paul D van der Linden ₁ , Rene Wiezer ₄ , Eric P A Van Dongen ₅ , Elke H J Krekels ₆ , Roger J M Brüggemann _{7,

8} , Catherijne A J Knibbe _{6,

9}

Affiliation

Background and Objective

Ciprofloxacin is a fluoroquinolone used for empirical and targeted therapy of a wide range of infections. Despite the increase in obesity prevalence, only very limited guidance is available on whether the ciprofloxacin dose needs to be adjusted when administered orally or intravenously in (morbidly) obese individuals. Our aim was to evaluate the influence of (morbid) obesity on ciprofloxacin pharmacokinetics after both oral and intravenous administration, to ultimately guide dosing in this population.

Methods

(Morbidly) obese individuals undergoing bariatric surgery received ciprofloxacin either orally (500 mg; n = 10) or intravenously (400 mg; n = 10), while non-obese participants received semi-simultaneous oral dosing of 500 mg followed by intravenous dosing of 400 mg 3 h later (n = 8). All participants underwent rich sampling (11–17 samples) for 12 h after administration. Non-linear mixed-effects modelling and simulations were performed to evaluate ciprofloxacin exposure in plasma. Prior data from the literature were subsequently included in the model to explore exposure in soft tissue in obese and non-obese patients.

Results

Overall, 28 participants with body weights ranging from 57 to 212 kg were recruited. No significant influence of body weight on bioavailability, clearance or volume of distribution was identified (all p > 0.01). Soft tissue concentrations were predicted to be lower in obese individuals despite similar plasma concentrations compared with non-obese individuals.

Conclusion

Based on plasma pharmacokinetics, we found no evidence of the influence of obesity on ciprofloxacin pharmacokinetic parameters; therefore, ciprofloxacin dosages do not need to be increased routinely in obese individuals. In the treatment of infections in tissue where impaired ciprofloxacin penetration is anticipated, higher dosages may be required.

Trial Registration

Registered in the Dutch Trial Registry (NTR6058).

中文翻译：

（病态）肥胖和非肥胖个体口服和静脉给药后环丙沙星的药代动力学：一项前瞻性临床研究

背景与目的

环丙沙星是一种氟喹诺酮类药物，用于多种感染的经验性和靶向治疗。尽管肥胖患病率增加，但对于（病态）肥胖个体在口服或静脉内给药时是否需要调整环丙沙星剂量的指导非常有限。我们的目的是评估（病态）肥胖对口服和静脉内给药后环丙沙星药代动力学的影响，以最终指导该人群的给药。

方法

（病态）接受减肥手术的肥胖个体接受环丙沙星口服（500 mg；n = 10）或静脉注射（400 mg；n = 10），而非肥胖参与者接受半同时口服给药 500 mg，然后静脉给药3 小时后 400 毫克（n = 8）。所有参与者在给药后 12 小时都进行了丰富的采样（11-17 个样本）。进行非线性混合效应建模和模拟以评估血浆中的环丙沙星暴露。随后将文献中的先前数据包含在模型中，以探索肥胖和非肥胖患者的软组织暴露情况。