Pharmacokinetics of dapsone in children

Mirochnick, Mark; Michaels, Marian G.; Clarke, Diana F.; Brena, Anne; Regan, Anne Marie; Pelton, Stephen I.

doi:10.1016/s0022-3476(06)80033-8

Cited by 18 publications

(7 citation statements)

References 6 publications

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“…The data on concentration of drug in plasma are similar to those previously reported for HIV-infected patients and indicate a high interpatient variability of dapsone pharmacokinetics in such a population (7,10,11,18,19). We found serum albumin and blood CD4 ϩ lymphocyte count to be among the factors which may be responsible for variability.…”

Section: Discussionsupporting

confidence: 87%

Penetration of dapsone into pulmonary lining fluid of human immunodeficiency virus type 1-infected patients

Cruciani¹,

Gatti²,

Mengoli³

et al. 1997

Antimicrob Agents Chemother

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We studied the penetration of dapsone into the epithelial lining fluid (ELF) of sixteen human immunodeficiency virus type 1-infected patients who had received the drug at a dose of 100 mg twice weekly as primary prophylaxis for Pneumocystis carinii pneumonia. Bronchoscopy, bronchoalveolar lavage (BAL), and venipuncture were performed for each patient at a specific time after administration of the last dose of dapsone. Dapsone concentrations in plasma and BAL were determined by high-performance liquid chromatography. The apparent volume of ELF recovered by BAL was determined by using urea as an endogenous marker. The mean concentrations of dapsone in ELF at 2 h (five patients), 4 h (three patients), 12 h (two patients), 24 h (three patients), and 48 h (three patients) were 0.95, 0.70, 1.55, 0.23, and 0.45 mg/liter, respectively, while concentrations in plasma were 1.23, 0.79, 1.31, 0.83, and 0.18 mg/liter, respectively. Dapsone concentrations in ELF were 76, 79, 115, 65, and 291% of those observed in plasma at the same times, respectively. These data show that dapsone is well distributed into ELF and that a twice-weekly 100-mg prophylactic regimen results in sustained concentrations in this compartment.

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Section: Discussionsupporting

confidence: 87%

Penetration of dapsone into pulmonary lining fluid of human immunodeficiency virus type 1-infected patients

Cruciani¹,

Gatti²,

Mengoli³

et al. 1997

Antimicrob Agents Chemother

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“…Ethanolic formulation of dapsone improves dissolution. However, administration of dapsone formulated with ethanol and cherry syrup to three HIV-infected children resulted in very low concentrations in plasma (20). Children were also administered dideoxyinosine and antacids.…”

Section: Discussionmentioning

confidence: 99%

“…This guideline has been inferred from the clinical experience for treatment of leprosy and dermatitis herpetiformis in pediatric patients (4), but it is not based on pharmacokinetic data obtained from the target patient category. Recently, a study reporting on the pharmacokinetics of dapsone in eight children, six of whom were HIV infected (20), revealed that the bioavailability (F) of dapsone may be formulation dependent. In fact, three of the HIV-infected children treated with an extemporaneous solution made by pulverizing dapsone tablets and dissolving them in ethanol and cherry syrup had negligible steady-state levels in plasma following the administration of an oral dose of 1 mg/ kg/day to one patient and the same dose by gastric tube to two patients.…”

Section: Human Immunodeficiency Virus (Hiv)-infected Children With Lomentioning

confidence: 99%

Pharmacokinetics of dapsone in human immunodeficiency virus-infected children

Gatti

Loy

Casazza

et al. 1995

Antimicrob Agents Chemother

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Dapsone, administered at various doses and schedules, has been proven to be a safe and effective alternative to trimethoprim-sulfamethoxazole for prevention of Pneumocystis carinii pneumonia (PCP) in adults with human immunodeficiency virus (HIV) infection. Dapsone is also recommended by the Centers for Disease Control for PCP prophylaxis in HIV-infected children. However, the suggested dosage regimen is based upon clinical experience with children with leprosy and dermatitis herpetiformis rather than pharmacokinetic and pharmacodynamic data obtained from the target patient population. In order to determine a rational dosage regimen that could be tested in clinical studies aimed at the evaluation of dapsone for the prevention of PCP in HIV-infected children, we studied the pharmacokinetics of dapsone following a 2-mg/kg of body weight oral dose in twelve HIV-positive children aged 9 months to 9 years. Plasma was collected at the following times after dapsone administration: 0, 2, 4, 6, 12, 24, 48, 72, and 96 h. The levels of dapsone in plasma were determined by high-performance liquid chromatography. Data were analyzed by noncompartmental methods. Expressed as means ؎ standard deviations (ranges), the pharmacokinetic parameters were as follows: peak concentration in plasma, 1.12 ؎ 0.48 (0.44 to 1.81) mg/liter; time to peak concentration in plasma, 3.8 ؎ 1.3 (2 to 6) h; half-life at elimination phase, 24.2 ؎ 7.1 (14.4 to 35.0) h; clearance from plasma divided by bioavailability (CL/F), 1.15 ؎ 0.67 (0.37 to 2.63) ml/min/kg; and volume of distribution divided by bioavailability (V/F), 2.25 ؎ 1.20 (1.00 to 4.57) liters/kg. Oral CL correlated negatively with age (r ‫؍‬ 0.614 and P ‫؍‬ 0.034), as did V (r ‫؍‬ 0.631 and P ‫؍‬ 0.028). As a consequence of the high interindividual variability in growth retardation, pharmacokinetic parameters correlated with measures of body development better than they did with age (e.g., for CL/F to height, r ‫؍‬ 0.765 and P ‫؍‬ 0.004, and for V/F to height, r ‫؍‬ 0.748 and P ‫؍‬ 0.005). Since oral CL from plasma and V were positively and highly correlated (r ‫؍‬ 0.898 and P ‫؍‬ 0.0001), a lower absolute F may be the cause, in part, of higher values for CL/F and V/F in smaller children. The results of this study warrant the testing of a 2-mg/kg dose of dapsone administered twice or thrice weekly to HIV-infected children. The monitoring of drug levels in plasma and dosage adjustment may be necessary for smaller children.

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“…The Division of AIDS (DAIDS)/NIAID Toxicity Table for Grading Severity of Adult Adverse Experiences (August, 1992) and the DAIDS Toxicity Tables for Grading Severity of Pediatric Adverse Experiences for Children ≤ 3 Months of Age and > 3 Months of Age (April 1994) were used to report adverse events for study subjects. 15 All toxicities were followed through resolution.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of an Increased Atazanavir Dose With and Without Tenofovir During the Third Trimester of Pregnancy

Kreitchmann

Best

Wang

et al. 2013

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Reduced atazanavir exposure has been demonstrated during pregnancy with standard atazanavir/ritonavir dosing. We studied an increased dose during the third trimester of pregnancy. Methods IMPAACT 1026s is a prospective, non-blinded pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including two cohorts (with or without tenofovir) receiving atazanavir/ritonavir 300/100 mg once daily during the 2nd trimester (2nd trim), 400/100 mg during the 3rd trimester (3rd trim) and 300/100 mg postpartum (PP). Intensive steady-state 24-hour pharmacokinetic profiles were performed. Atazanavir concentrations were measured by HPLC. Pharmacokinetic targets were the 10th percentile atazanavir AUC (29.4 mcg*hr/mL) in non-pregnant adults on standard dose and 0.15 mcg/mL, minimum trough concentration. Results Atazanavir pharmacokinetic data were available for 37 women without tenofovir, 35 with tenofovir; Median (range) pharmacokinetic parameters are presented for 2nd, 3rd trim and PP and number who met target/total. * indicates p<0.05 compared to PP. Atazanavir without tenofovir AUC 30.5 (9.19–93.8), 45.7 (11–88.3), and 48.8 (9.9–112.2) mcg-hr/mL, and 8/14, 29/37 and 27/34 met target. C24h was 0.49 (0.09–4.09), 0.71 (0.14–2.09), and 0.90 (0.05–2.73) mcg/mL; 13/14, 36/37 and 29/34 met target. Atazanavir with tenofovir AUC 26.2 (6.8–60.9)*, 37.7 (0.72–88.2)*, and 58.6 (6–149) mcg-hr/mL, and 7/17, 23/32 and 27/29 met target. C24h was 0.44 (0.12–1.06)*, 0.57 (0.02–2.06)*, and 1.26 (0.09–5.43) mcg/mL; 7/17, 23/32 and 27/29 met target. Atazanavir/ritonavir was well tolerated with no unanticipated adverse events. Conclusions Atazanavir/ritonavir increased to 400/100mg provides adequate atazanavir exposure during the third trimester and should be considered during the second trimester.

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Pharmacokinetics of dapsone in children

Cited by 18 publications

References 6 publications

Penetration of dapsone into pulmonary lining fluid of human immunodeficiency virus type 1-infected patients

Penetration of dapsone into pulmonary lining fluid of human immunodeficiency virus type 1-infected patients

Pharmacokinetics of dapsone in human immunodeficiency virus-infected children

Pharmacokinetics of an Increased Atazanavir Dose With and Without Tenofovir During the Third Trimester of Pregnancy

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