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10.1002/jps.24505

http://scihub22266oqcxt.onion/10.1002/jps.24505
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C4536115!4536115!26010239
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suck abstract from ncbi


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pmid26010239      J+Pharm+Sci 2015 ; 104 (9): 3229-35
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  • Few Drugs Display Flip-Flop Pharmacokinetics and These Are Primarily Associated with Classes 3 and 4 of the BDDCS #MMPMID26010239
  • Garrison KL; Sahin S; Benet LZ
  • J Pharm Sci 2015[Sep]; 104 (9): 3229-35 PMID26010239show ga
  • Purpose: To determine the number of drugs exhibiting flip-flop pharmacokinetics following oral dosing from immediate release dosage forms and if they exhibit a common characteristic that may be predicted based on BDDCS classification. Method: The literature was searched for drugs displaying flip-flop kinetics (i.e. absorption half-life larger than elimination half-life) in mammals in PubMed, via internet search engines and reviewing drug pharmacokinetic data. Results: Twenty two drugs were identified as displaying flip-flop kinetics in humans (13 drugs), rat (9 drugs), monkey (3 drugs), horse (2 drugs), and/or rabbit (2 drugs). Nineteen of the 22 drugs exhibiting flip-flop kinetics were BDDCS Classes 3 and 4. One of the three exceptions, meclofenamic acid (Class 2), was identified in the horse however it would not exhibit flip-flop kinetics in humans where the oral dosing terminal half-life is 1.4 hr. The second, carvedilol, can be explained based on solubility issues, but the third sapropterin dihydrochloride (nominally Class 1) requires further consideration. Conclusion: The few drugs displaying oral flip-flop kinetics in humans are predominantly BDDCS Classes 3 and 4. New molecular entities predicted to be BDDCS Classes 3 and 4 could be liable to exhibit flip-flop kinetics when the elimination half life is short and should be suspected to be substrates for intestinal transporters.
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