ArticlePharmaceutical research2005
pH-dependent dissolution in vitro and absorption in vivo of weakly basic drugs: development of a canine model.
Article in Pharmaceutical research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 117 citations in OpenAlex.
- The effect of pH stability and aqueous solubility on the oral bioavailability of a novel antileishmanial agent.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2026Article
- Impact of Gastric Emptying Kinetics on Dipyridamole Dissolution Using a Gastrointestinal Simulator.The AAPS journal · 2025Article
- Integrated approach to reducing polypharmacy in older people: exploring the role of oxidative stress and antioxidant potential therapy.Redox report : communications in free radical research · 2024Review
- Rational use of gastroprotectants in cats: An evidence-based approach.Journal of feline medicine and surgery · 2024Review
- Hydroxylated Coumarin-Based Thiosemicarbazones as Dual Antityrosinase and Antioxidant Agents.International journal of molecular sciences · 2023Article
- Fast-Fed Variability: Insights into Drug Delivery, Molecular Manifestations, and Regulatory Aspects.Pharmaceutics · 2022Review
- An IQ Consortium Perspective on Connecting Dissolution Methods to In Vivo Performance: Analysis of an Industrial Database and Case Studies to Propose a Workflow.The AAPS journal · 2022Article
- Predicting the Drug-Drug Interaction Mediated by CYP3A4 Inhibition: Method Development and Performance Evaluation.The AAPS journal · 2021Article
- Effect of CYP3A4 Inhibitors and Inducers on Pharmacokinetics and Pharmacodynamics of Saxagliptin and Active Metabolite M2 in Humans Using Physiological-Based Pharmacokinetic Combined DPP-4 Occupancy.Frontiers in pharmacology · 2021Article
- Understanding the Effect of Hydroxypropyl-β-Cyclodextrin on Fenebrutinib Absorption in an Itraconazole-Fenebrutinib Drug-Drug Interaction Study.Clinical pharmacology and therapeutics · 2020Article
- Utilization of In Vitro, In Vivo and In Silico Tools to Evaluate the pH-Dependent Absorption of a BCS Class II Compound and Identify a pH-Effect Mitigating Strategy.Pharmaceutical research · 2019Article
- ACVIM consensus statement: Support for rational administration of gastrointestinal protectants to dogs and cats.Journal of veterinary internal medicine · 2018Article
- Cocrystals Mitigate Negative Effects of High pH on Solubility and Dissolution of a Basic Drug.Crystal growth & design · 2018Article
- Article
- Reverse screening approach to identify potential anti-cancer targets of dipyridamole.American journal of translational research · 2016Article
- From bench to humans: formulation development of a poorly water soluble drug to mitigate food effect.AAPS PharmSciTech · 2014Article
- pH-Induced precipitation behavior of weakly basic compounds: determination of extent and duration of supersaturation using potentiometric titration and correlation to solid state properties.Pharmaceutical research · 2012Article
- Prediction of modified release pharmacokinetics and pharmacodynamics from in vitro, immediate release, and intravenous data.The AAPS journal · 2009Article
- Current methods for predicting human food effect.The AAPS journal · 2008Review
- Application of gastrointestinal simulation for extensions for biowaivers of highly permeable compounds.The AAPS journal · 2008Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe aim of this research was to develop a pH-dependent canine absorption model for studying pH effect on both dissolution in vitro and pharmacokinetics in vivo using the weak bases ketoconazole and dipyridamole as model drugs.
methodsKetoconazole and dipyridamole pH-dependent dissolution profiles in vitro were determined by dissolution test at different pH values using USP apparatus II and an Opt-Diss Fiber Optic UV System. In vivo absorption studies for ketoconazole and dipyridamole were performed with crossover design in three groups of beagle dogs under control (no treatment), pentagastrin, and famotidine treatments. Ketoconazole and dipyridamole plasma concentrations were quantified by gradient high performance liquid chromatography mass spectroscopy (HPLC MS/MS). Pharmacokinetic parameters were determined from individual plasma concentration vs. time profiles.
resultsKetoconazole and dipyridamole displayed pH-dependent dissolution. Increasing the pH of the dissolution medium from 1.2 to 6.8 reduced the extent of dissolution of ketoconazole and dipyridamole at 1 h by 96% and 92%, respectively. In vivo studies in dogs under control (no treatment), pentagastrin, and famotidine treatments show marked differences in systemic ketoconazole and dipyridamole exposure. Area under the concentration-time curve (AUC) increased more than 4-fold as compared to control group, whereas it increased nearly 30-fold for ketoconazole and 9-fold for dipyridamole with pentagastrin (gastric pH approximately 2-3) as compared to famotidine (gastric pH approximately 5-7.5) treatment.
conclusionsThis work demonstrates a pH-dependent dissolution in vitro and absorption in vivo for the weak bases ketoconazole and dipyridamole independent of food effects. This model is useful to examine pH-dependent effects on oral drug absorption and for screening formulations to overcome the pH dependency.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.