Flip-flop kinetics

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In pharmacokinetics, flip-flop phenomenon happens when a drug is released at a sustained rate instead of immediate release, such as sustained-release formulation vs. immediate-release formulation (tablet, IV).

In flip-flop kinetics, ka (absorption constant) is much slower than ke (elimination constant).[1] This apparent difference shift the slope of log Cp vs time curve in which now the apparent part of ke looks much smaller than it is if the drug is administered intravenously or by immediate-release formulation. The part of downward curve becomes a reflection of actual ka while the upward part of the curve is the actual representation of ke. That "flip-flop" part of curve is the so-called flip-flop kinetics.

The application of flip-flop kinetics is very important in the development of sustained-release and controlled-release formulation in pharmaceutical manufacturing.

References[edit]

https://www.ualberta.ca/~csps/JPPS1%283%29/H.Boxenbaum/flip-flop.htm

  1. Wagner J G; Nelson E. Kinetic analysis of blood levels and urinary excretion in the absorptive phase after single doses of drug. J Pharm Sci, 53:1392–1403, 1964.
  2. Wagner J G. Pharmacokinetic absorption plots from oral data alone or oral/intravenous data and an exact Loo–Riegelman equation. J Pharm Sci, 72:838–842, 1983.
  3. Katakam M; Ravis W R; Golden D L; Banga A K. Controlled release of human growth hormone following subcutaneous administration in dogs. Int J Pharm, 152:53–58, 1997.