Kinetic Characterization of Secretory Transport of a New Ciprofloxacin Derivative (CNV97100) across Caco-2 Cell Monolayers**This work has been submitted for the partial fulfillment of the requirement for a Ph.D. Degree in Pharmaceutics at the University of Valencia, Valencia, Spain

Ruiz-Garcı́a, Ana; Lin, Huimin; Plá-Delfina, J.M.; Hu, Ming

doi:10.1002/jps.10244

Cited by 24 publications

(3 citation statements)

References 34 publications

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“…Many in vitro and animal studies emphasize the importance of drug transporters (including P-glycoprotein) for quinolone antibiotics at the renal, hepatobiliary, and intestinal sites [1,2,3,4,5,6,7,8,9]. Fluoroquinolones are both subject to renal tubular secretion and reabsorption, and either of these processes may be subject to drug-drug interactions [9,10,11,12,13,14,15].…”

Section: Introductionmentioning

confidence: 99%

Population Pharmacokinetics and Penetration into Prostatic, Seminal, and Vaginal Fluid for Ciprofloxacin, Levofloxacin, and Their Combination

et al. 2011

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Background: Our objectives were to assess the pharmacokinetic interaction and body fluid penetration of ciprofloxacin and levofloxacin. Methods: This study was a single-dose open randomized three-way crossover in 15 healthy volunteers receiving 500 mg oral levofloxacin, 500 mg oral ciprofloxacin, or 250 mg levofloxacin and 250 mg ciprofloxacin co-administered. Serum, urine, and body fluid concentrations were determined by high-performance liquid chromatography and analyzed via population pharmacokinetic modeling. Results: Modeling indicated that ciprofloxacin inhibited the renal reabsorption of levofloxacin. Ciprofloxacin increased the net renal clearance of levofloxacin by 13%, as its estimated affinity for a putative tubular reabsorption transporter was 12-fold higher (Km: 568 µM) compared to levofloxacin (Km: 6,830 µM). Levofloxacin increased the bioavailability of ciprofloxacin by 12% and achieved significantly (p < 0.05) higher concentrations at 3 h in ejaculate, prostatic, seminal, and vaginal fluid compared to ciprofloxacin. Conclusion: Modeling suggested that ciprofloxacin inhibited the tubular reabsorption of levofloxacin due to a 12-fold higher affinity for a putative tubular reabsorption transporter compared to levofloxacin. This pharmacokinetic interaction was not clinically relevant.

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Section: Introductionmentioning

confidence: 99%

Population Pharmacokinetics and Penetration into Prostatic, Seminal, and Vaginal Fluid for Ciprofloxacin, Levofloxacin, and Their Combination

et al. 2011

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“…The advantage of selecting this specific dataset is that the data have been obtained in the same experimental conditions. To verify how representative our dataset is, we collected data for 131 compounds available in the literature for a total of 277 Caco-2 cell permeability values (different values have been obtained for a number of these drugs in different experimental conditions) ( Artursson, 1990 ; Artursson and Karlsson, 1991 ; Artursson and Magnusson, 1990 ; Augustijns et al , 1996 ; Aungst et al , 2000 ; Chong et al , 1997 ; Collett et al , 1996 ; Gres et al , 1998 ; Haeberlin et al , 1993 ; Hilgendorf et al , 2000 ; Hou et al , 2004 ; Hovgaard et al , 1995 ; Lentz et al , 2000 ; Liang et al , 2000 ; Rubas et al , 1993 ; Ruiz-Garcia et al , 2002 ; Saha and Kou, 2002 ; Schipper et al , 2001 ; Wu et al , 2000 ; Yee 1997 ; Zhu et al , 2002 ) and compared both their Caco2 experimental values ( Supplementary Figure S1 ) and their structural features.…”

Section: Methodsmentioning

confidence: 99%

Prediction of the permeability of neutral drugs inferred from their solvation properties

2015

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Motivation: Determination of drug absorption is an important component of the drug discovery and development process in that it plays a key role in the decision to promote drug candidates to clinical trials. We have developed a method that, on the basis of an analysis of the dynamic distribution of water molecules around a compound obtained by molecular dynamics simulations, can compute a parameter-free value that correlates very well with the compound permeability measured using the human colon adenocarcinoma (Caco-2) cell line assay.Results: The method has been tested on twenty-three neutral drugs for which a consistent set of experimental data is available. We show here that our method reproduces the experimental data better than other existing tools. Furthermore it provides a detailed view of the relationship between the hydration and the permeability properties of molecules.Contact: anna.tramontano@uniroma1.itSupplementary information: Supplementary data are available at Bioinformatics online.

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“…Permeability studies were conducted with an orbital shaking (50 rpm) and with pH 7.0 in both chambers. Standard protocols were described and validated previously in our laboratory [12][13][14][15][16]. Four samples of 200 µL were taken and replaced with a fresh buffer from the receiver side at 15, 30, 45, and 90 min.…”

Section: Permeability Assays: Cell Culture and Transport Studiesmentioning

confidence: 99%

Investigation to Explain Bioequivalence Failure in Pravastatin Immediate-Release Products

et al. 2019

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The purpose of this work is to explore the predictive ability of the biopharmaceutics classification system (BCS) biowaiver based on the dissolution methods for two pravastatin test products, where one of them showed bioequivalence (BE) while the other test failed (non-bioequivalence, or NBE), and to explore the reasons for the BE failure. Experimental solubility and permeability data confirmed that pravastatin is a BCS class III compound. The permeability experiments confirmed that the NBE formulation significantly increased pravastatin permeability, and could explain its higher absorption rate and higher Cmax. This finding highlights the relevance of requiring similar excipients for BCS class III drugs. The BCS-based biowaiver dissolution tests at pH 1.2, 4.5, and 6.8, with the paddle apparatus at 50 rpm in 900 mL media, were not able to detect differences in pravastatin products, although the NBE formulation exhibited a more rapid dissolution at earlier sampling times. Dissolution tests conducted in 500 mL did not achieve complete dissolution, and both formulations were dissimilar because the amount dissolved at 15 min was less than 85%. The difference was less than 10% at pH 1.2 and 4.5, while at pH 6.8 f2, results reflected the Cmax rank order.

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Kinetic Characterization of Secretory Transport of a New Ciprofloxacin Derivative (CNV97100) across Caco-2 Cell Monolayers**This work has been submitted for the partial fulfillment of the requirement for a Ph.D. Degree in Pharmaceutics at the University of Valencia, Valencia, Spain

Cited by 24 publications

References 34 publications

Population Pharmacokinetics and Penetration into Prostatic, Seminal, and Vaginal Fluid for Ciprofloxacin, Levofloxacin, and Their Combination

Population Pharmacokinetics and Penetration into Prostatic, Seminal, and Vaginal Fluid for Ciprofloxacin, Levofloxacin, and Their Combination

Prediction of the permeability of neutral drugs inferred from their solvation properties

Investigation to Explain Bioequivalence Failure in Pravastatin Immediate-Release Products

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