Regarding Dapsone.. Absorption and Metabolism

shevyatiwari's version from 2015-10-26 10:28

Section 1

Question Answer
Derived from SulfonamidesF. Drug category Sulfone
Highly HydrophilicF. Highly lipophilic - penetrates into cells, breast milk and various tissues
Poorly absorbed from the gutF. Well absorbed from gut 70-80% bioavailbaility
Peak concentration reached in 28 hoursF. Peak conc in tissue in 2-8 hours
99% protein bound F. highly protein bound at 70-90%. c/f sulfapyridine 50-70%
Elimination half life average 24-26hrsT. Range 10-50hrs
Can remain in blood for 30 days after a single oral doseT. Due to SIGNIFICANT ENTEROHEPATIC CIRCULATION and strong protein binding of Dapsone and Metabolite MADDS
No major metabolitesF. Major metabolite MONO-ACETYLDAPSONE MADDDS
Increased effectiveness compared to other sulfonamides and sulfones due toSuperior absorption from gut and effective penetration into cells - lipophilic.
Water soluble F. Not water soluble
Does not cross the placenta but is secreted in breast milk.F. Does BOTH. Crosses the placenta and secreted in breast milk. highly lipophilic
Hemolysis not seen in nursing infants and mothers taking dapsoneF. Haemolysis seen in nursing mothers and infants taking dapsone
No harmful effects demonstrated on fetusT. But preg. Cat C

Section 2

Question Answer
Primarily metabolised via acetylation F. Metabolised in 2 WAYS. N-acetylation and N-HYDROXYLATION
Acetylated in the liver to diacetyldapsone F. acetylated in the liver by N-ACETYLTRANSFERASE to MONOacetyldapsone MADDS
MADDS deacetylated back to diamino di phenylsulfone (44,DADPS) - aka dapsoneTrue
Variability in acetylator status affects metabolism False.
Initital acetylation is reversibleTrue
Need to check acetylator status prior to commencing DapsoneFalse. Not required - does not affect metabolism
During early phase of absorption increased ratio of MADDS/DDS is absorbedTrue probably due to stronger protein binding of MADDS than Dapsone DDS
N-hydroxylation occurs as the first step in the kidneyFalse, Second major metabolic pathway. In liver
Hydroxylation not affected by CYP 450F . Various Cytochrome enzymes involved 3A4, 2E1, 2C9
N-Acetylated metabolites DDS-NOH thought to be resposible for hematological adverse effectsF. N - HYDROXYLATION metabolite DDS-NOH causes methemoglobulinaemia and haemolyic anamia
N- hydroxylation CAN be inhibited by use of cimetidineT. Reduces methemoglobulinaemia without reducing plasma levels of dapsone