(Redirected from Flip-flop kinetics )
Flip–flop kinetics , or flip–flop pharmacokinetics , describes an atypical situation in pharmacokinetics where a drug's rate of absorption or the rate at which it enters the bloodstream is slower than its elimination rate. That is, when the k a (absorption constant ) is slower than k e (elimination constant ).
These circumstances can occur with sustained-release formulations, depot injections , and some subcutaneous or intradermal injections . In the resulting slope of log plasma concentration (log Cp) versus time, the apparent k e is determined by the k a , and the apparent k e is smaller than when the drug is administered intravenously or by immediate-release formulation. Depot injections such as depot antipsychotics and long-acting injectable steroid hormone medications like estradiol valerate , testosterone enanthate , and medroxyprogesterone acetate are examples of drugs with flip–flop kinetics.
The term "flip–flop" indicates that the downward slope more closely represents k a rather than k e .
Flip–flop kinetics can create difficulties in the determination and interpretation of pharmacokinetic parameters if not recognized.
References
^ Yáñez JA, Remsberg CM, Sayre CL, Forrest ML, Davies NM (May 2011). "Flip-flop pharmacokinetics--delivering a reversal of disposition: challenges and opportunities during drug development" . Ther Deliv . 2 (5): 643–72. doi :10.4155/tde.11.19 . PMC 3152312 . PMID 21837267 .
^ Toutain PL, Bousquet-Mélou A (December 2004). "Plasma terminal half-life". Journal of Veterinary Pharmacology and Therapeutics . 27 (6): 427–39. doi :10.1111/j.1365-2885.2004.00600.x . PMID 15601438 .
Determination of Absorption Rate Constant
Spanarello S, La Ferla T (2014). "The pharmacokinetics of long-acting antipsychotic medications". Curr Clin Pharmacol . 9 (3): 310–7. doi :10.2174/15748847113089990051 . PMID 23343447 .
Jann MW, Ereshefsky L, Saklad SR (1985). "Clinical pharmacokinetics of the depot antipsychotics". Clin Pharmacokinet . 10 (4): 315–33. doi :10.2165/00003088-198510040-00003 . PMID 2864156 . S2CID 12848774 .
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