Dapsone pharmacokinetics

Lee BL, Safrin S, Makrides V, Gambertogho JG. Zidovudine, trimethoprim, and dapsone pharmacokinetic interactions in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother 1996 40(5) 1231-6. 

Sahai J, Garber G, Gallicano K, Oliveras L, CameronDW. Effects of the antacids in didanosine tablets on dapsone pharmacokinetics. Arm Intern Med( 995) 123,584-7. 

N. L. Pochopin, W. N. Charman, V. J. Stella, Pharmacokinetics of Dapsone and Amino Acid Prodrugs of Dapsone , Drug Metab. Dispos. 1994, 22, 770-777 N. L. Pochopin, W. N. Charman, V. J. Stella, Amino Acid Derivatives of Dapsone as Water-Soluble Prodrugs , Int. J. Pharm. 1995, 121, 157-167. 

When thionamides are used in combination with rifam-picin, hepatotoxicity is more common and severe (18,19). There was a 13% incidence of hepatotoxicity in patients with multibaciUary leprosy treated with dap-sone, rifampicin, and protionamide 10 mg/kg/day, and a 17% incidence in 110 patients treated with dapsone, rifampicin, and protionamide 5 mg/kg/day however, although the lower dose of protionamide did not reduce the incidence of hepatotoxicity, it did reduce its severity (20). Protionamide does not affect the pharmacokinetics of rifampicin (21). 

Zuidema J, Hilbers-Modderman ES, Merkus FW. Clinical pharmacokinetics of dapsone. Clinical pharmacokinetics. 1986 Jul-Aug 11(4) 299-315. 

Classification and pharmacokinetics The antifolate group includes pyrimethamine, proguanil, sulfadoxine, and dapsone. All of these drugs are absorbed orally and are excreted in the urine, partly in unchanged form. Proguanil has a shorter half-life (12-16 hours) than other drugs in this subclass (half-life > 100 hours). 

Koda RT, Dube MP, Li WY, et al. Pharmacokinetics of trimetrexate and dapsone in AIDS patients with Pneumocystis carinii pneumonia. J Clin Pharmacol 1999 39 268-274. 

D. Pharmacokinetics. Absorption of dapsone is delayed peak plasma levels occur between 4 and 8 hours after ingestion. The volume of distribution (Vd) is 1.5 Ukg. Protein binding is approximately 70-90%. Dapsone is metabolized by two primary routes, acet ation and P-450 oxidation. Both dapsone and its acetylated metabolite undergo enterohepatic recirculation. The average elimination half-life is 30 hours after a therapeutic dose and as long as 77 hours after an overdose. (See also Table 11-59.)... 

Dapsone does not significantly affect the pharmacokinetics of aspirin. 

A comparison of the pharmacokinetics of aspirin in 8 healthy subjects and 8 patients with uncomplicated lepromatous leprosy found that the pharmacokinetics of a single 600-mg dose of aspirin was not affected by either leprosy, or by treatment with dapsone 100 mg daily for 8 days. No special precautions would seem likely to be needed on concurrent use. 

Garg SK, Kumar B, Shukla VK, Bakaya V, Lai R, Kaur S. Pharmacokinetics of aspirin and chloramphenicol in normal and leprotic patients before and after dapsone therapy. IntJ Clin Pharmacol Ther Toxicol (1988) 26, 204-5. 

Dapsone can reduce the anti-inflammatory effects of clofazimine. Clofazimine does not affect the pharmacokinetics of dapsone. 

Venkatesan K, Mathur A, Girdhar BK, Bharadwaj VP. The effect of clofazimine on the pharmacokinetics of rifampiein and dapsone in leprosy. JAntimicrob Chemother (1986) 18, 715-18. 

Pieters FAJM, Woonink F, Zuidema J. Influence of once-monthly rifampiein and daily clofazimine on the pharmacokinetics of dapsone in lepro patients in Nigeria. EurJ Clin Pharmacol (1988) 34, 73-6. 

No pharmacokinetic interaction appears to occur between dapsone and proguanil, and they have been successfully used together for malaria prophylaxis. 

Pyrimethamine does not significantiy affect the pharmacokinetics of dapsone. 

Ahmad RA, Rogers HJ. Pharmacokinetics and protein binding interactions of dapsone and pyrimethamine. BrJ Clin Pharmacol (1980) 10, 9-24. 

Falloon J, Lavelle J, Ogata-Arakaki D, Byrne A, Graziani A, Morgan A, AmanteaMA, Ownby K, Polls M, Davey RT, Kovacs JA, Lane HC, Masur H, MacGregor RR. Pharmacokinetics and safety of weekly dapsone and dapsone plus pyrimethamine for prevention of pneumocystis pneumonia. Antimicrob Agents Chemother ( 994) 38, 1580-7. 

A study in 7 patients with leprosy given single doses of dapsone 100 mg and rifampici n 600 mg, alone or together, found that while the pharmacokinetics of rifampicin were not significantly changed, the half-life of the dapsone was roughly halved and the AUC was reduced hy about 20%. ... 

Jaundice, liver damage and deaths have occurred in other leprosy patients given rifampicin and protionamide or ethionamide. Protionamide does not affect the pharmacokinetics of either dapsone or rifampicin. ... 

Mehta J, Gandhi IS, Sane SB, Wamburkar MN. Effect of clofazimine and dapsone on rifampicin (Lositril) pharmacokinetics inmultibacillary andpaucibacillary leprosy cases. Indian JLepr( 9S5)57, 297-310. 

Buffered didanosine does not alter the pharmacokinetics of dapsone, but there is some circumstantial evidence to suggest that it may reduce the prophyiactic effects of dapsone in preventing Pneumocystis pneumonia. Dapsone has no effect on the pharma-... 

A pharmacokinetic study in 12 TUV-positive patients who were given zalcitabine 1.5 mg three times daily and dapsone 100 mg daily, alone or together, found that dapsone did not significantly affect the kinetics of the zalcitabine. However, zaleitabine deeieased the clearance of dapsone by 21%, increased its maximum serum levels by 19% and increased its half-life by 34%. These changes are relatively small and seem unlikely to have much clinical relevance, but until this is confirmed it would seem prudent to monitor the concurrent use of these two drugs. The UK manufacturer recommended caution with the combination because of the possibility of an increased risk of peripheral neuropathy the US manufacturer advised avoiding the combination where possible. ... 

Dapsone 100 mg daily had no effect on the pharmacokinetics of a single 200-mg dose of zidovudine in 8 TUV-positive subjects. In a further study, which considered the safety of dapsone in combination with zidovudine, dapsone was shown to increase the risk of zidovudine-related blood dys-crasias. Therefore it would seem that dapsone and zidovudine can be given concurrently, but monitoring for an increase in adverse events would seem advisable. 

Lee BL, Tauber MG, Chambers HF, Gamberto io J, Delahunty T. Zalcitabine (DDC) and dapsone (DAP) pharmacokinetic (PK) interaction in HIV-infected patients. Clin Pharmacol Ther (199 57, 186. 

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