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 ka is slower than ke.
These circumstances can occur with sustained-release formulations, depot injections, and some subcutaneous or intradermal injections. In the resulting slope of log plasma concentration 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.
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.