ReviewTherapeutic delivery2011
Flip-flop pharmacokinetics--delivering a reversal of disposition: challenges and opportunities during drug development.
Review in Therapeutic delivery, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
128 citing papers in PubMed.
- TLD-1, a Novel Liposomal Doxorubicin, in Patients with Solid Tumors: Comparative Pharmacokinetics and Final Results of a Multicenter Phase 1 Study (SAKK 65/16).Clinical pharmacokinetics · 2026Trial
- Evaluation of pharmacokinetic interactions between long-acting cabotegravir or emtricitabine/tenofovir disoproxil fumarate and hormonal contraceptive agents: a tertiary analysis of South African participants in HPTN 084.Journal of the International AIDS Society · 2025Trial
- A Randomized Phase 1 Study Evaluating Pharmacokinetics, Safety, and Tolerability of a High-Concentration, Long-Acting Cabotegravir Formulation in Adults Without HIV.Clinical pharmacology in drug development · 2025Trial
- Pharmacokinetics and Lung Deposition After Administration of Inhaled Mosliciguat (BAY 1237592): Results from Randomized Phase I Studies in Healthy Men.Clinical pharmacokinetics · 2025Trial
- Pharmacokinetic and Safety Profiles of MIT-001, a Novel Ferroptosis Inhibitor, After Subcutaneous Administration in Healthy Participants.Drug design, development and therapy · 2025Trial
- Pharmacologic evaluation of delayed long-acting cabotegravir administration among cisgender women in HPTN 084.Antimicrobial agents and chemotherapy · 2024Trial
- Trial
- Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing.Antimicrobial agents and chemotherapy · 2018Trial
- Population Pharmacokinetic/Pharmacodynamic Modeling of Depot Testosterone Cypionate in Healthy Male Subjects.CPT: pharmacometrics & systems pharmacology · 2018Trial
- Evaluation of pharmacokinetic model designs for subcutaneous infusion of insulin aspart.Journal of pharmacokinetics and pharmacodynamics · 2017Trial
- Pharmacokinetics, Safety, and Tolerability of Single-Dose Intravenous (ZTI-01) and Oral Fosfomycin in Healthy Volunteers.Antimicrobial agents and chemotherapy · 2017Trial
- Population-Based Pharmacokinetic and Exposure-Efficacy Analyses of Peginterferon Beta-1a in Patients With Relapsing Multiple Sclerosis.Journal of clinical pharmacology · 2017Trial
- Clinical Predictors of Venetoclax Pharmacokinetics in Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma Patients: a Pooled Population Pharmacokinetic Analysis.The AAPS journal · 2016Trial
- Trial
- Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses.Acta veterinaria Scandinavica · 2013Trial
- Engineering a self-protecting dermal filler: active hyaluronidase inhibition extends theRSC advances · 2026Article
- One-Dose Efficacy of Long-Acting Sorfequiline in a Mouse Model of Tuberculosis Preventive Therapy.bioRxiv : the preprint server for biology · 2026Article
- Long-Acting Therapeutics in Pediatric Health: Bridging Innovation and Access.Clinical pharmacology and therapeutics · 2026Review
- Article
- Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
Flip-flop pharmacokinetics is a phenomenon often encountered with extravascularly administered drugs. Occurrence of flip-flop spans preclinical to human studies. The purpose of this article is to analyze both the pharmacokinetic interpretation errors and opportunities underlying the presence of flip-flop pharmacokinetics during drug development. Flip-flop occurs when the rate of absorption is slower than the rate of elimination. If it is not recognized, it can create difficulties in the acquisition and interpretation of pharmacokinetic parameters. When flip-flop is expected or discovered, a longer duration of sampling may be necessary in order to avoid overestimation of fraction of dose absorbed. Common culprits of flip-flop disposition are modified dosage formulations; however, formulation characteristics such as the drug chemical entities themselves or the incorporated excipients can also cause the phenomenon. Yet another contributing factor is the physiological makeup of the extravascular site of administration. In this article, these causes of flip-flop pharmacokinetics are discussed with incorporation of relevant examples and the implications for drug development outlined.
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Registered trials
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.