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.[1][2] That is, when the ka (absorption constant) is slower than ke (elimination constant).

These circumstances can occur with sustained-release formulations, depot injections, and some subcutaneous or intradermal injections.[3] In the resulting slope of log plasma concentration (log Cp) versus time, the apparent ke is determined by the ka, and the apparent ke 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.[4][5]

The term "flip–flop" indicates that the downward slope more closely represents ka rather than ke.

Flip–flop kinetics can create difficulties in the determination and interpretation of pharmacokinetic parameters if not recognized.[1][2]

References
  1. 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.
  2. 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.
  3. Determination of Absorption Rate Constant
  4. 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.
  5. 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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