The Pharmacokinetics and Acceptability of Lopinavir/Ritonavir Minitab Sprinkles, Tablets, and Syrups in African HIV-Infected Children

Musiime, Victor; Fillekes, Quirine; Kekitiinwa, Addy; Kendall, Lindsay; Keishanyu, R.; Namuddu, R.; Young, Nancy L.; Opilo, Wilfred; Lallemant, Marc; Walker, A. Sarah; Burger, David M.; Gibb, Diana

doi:10.1097/qai.0000000000000135

Cited by 59 publications

(64 citation statements)

References 8 publications

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“…Recently approved integrase inhibitors and protease inhibitors with better safety profiles and dosage intervals are competing as preferred first-line regimens. A summary of recently approved antiretroviral drugs is provided in Table 2 [40][41][42][43][44][45][46][47][48][49][50][51][52][53]. Tenofovir has been licensed for children >2 years of age at 8 mg/kg daily.…”

Section: Retention In Care and Antiretroviral Therapymentioning

confidence: 99%

An update on the HIV treatment cascade in children and adolescents

Bobat

Archary²,

Lawler³

2015

Current Opinion in HIV and AIDS

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Section: Retention In Care and Antiretroviral Therapymentioning

confidence: 99%

An update on the HIV treatment cascade in children and adolescents

Bobat

Archary²,

Lawler³

2015

Current Opinion in HIV and AIDS

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“…As part of a recent clinical study, Musiime et al reported that older children aged 4 to 13 years old who were able to swallow tablets found these more acceptable than 265 mini-tablets that were administered with food (Musiime et al, 2014). Problems with taste and swallowing difficulties were reported by 50% and 13% of the cohort respectively for the mini-tablet product, while neither problem was reported with tablets.…”

Section: Novel Dosage Formsmentioning

confidence: 99%

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children’s Acceptability of Oral Formulations (CALF) Study

Ranmal¹,

Cram

Tuleu³

2016

International Journal of Pharmaceutics

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A lack of evidence to guide the design of age-appropriate and acceptable dosage forms has been a longstanding knowledge gap in paediatric formulation development. The Children's Acceptability of Oral Formulations (CALF) study captured end-user perceptions and practices with a focus on solid oral dosage forms, namely tablets, capsules, chewables, orodispersibles, multiparticulates (administered with food) and mini-tablets (administered directly into the mouth). A rigorous development and testing phase produced age-adapted questionnaires as measurement tools with strong evidence of validity and reliability. Overall, 590 school children and adolescents, and 428 adult caregivers were surveyed across hospitals and various community settings. Attitudes towards dosage forms primarily differed based on age and prior use. Positive attitudes to tablets and capsules increased with age until around 14 years. Preference was seen for chewable and orodispersible preparations across ages, while multiparticulates were seemingly less favourable. Overall, 59.6% of school children reported willingness to take 10mm diameter tablets, although only 32.1% of caregivers perceived this size to be suitable. While not to be taken as prescriptive guidance, the results of this study provide some evidence towards rational dosage form design, as well as methodological approaches to help design tools for further evaluation of acceptability within paediatric studies.

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“…Of note, a higher percentage of missed medication doses was estimated in the LPV/r group than the 3TC group (26% for the LPV/r group versus 11% for the 3TC group). This may be explained, in part, by the fact that the LPV/r syrup formulation is often described to have an unpleasant taste (16). After exclusion of the data for samples from infants that may Our study shows that none of the HIV-exposed infants whose values were below the therapeutic pharmacokinetic target acquired HIV infection during the trial period.…”

Section: Discussionmentioning

confidence: 88%

Are Prophylactic and Therapeutic Target Concentrations Different?: the Case of Lopinavir-Ritonavir or Lamivudine Administered to Infants for Prevention of Mother-to-Child HIV-1 Transmission during Breastfeeding

Foissac

Blume

Tréluyer

et al. 2017

Antimicrob Agents Chemother

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The ANRS 12174 trial assessed the efficacy and tolerance of lopinavir (LPV)-ritonavir (LPV/r) prophylaxis versus those of lamivudine (3TC) prophylaxis administered to breastfed infants whose HIV-infected mothers were not on antiretroviral therapy. In this substudy, we assessed LPV/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at weeks 6, 26, and 38 of life. We applied a Bayesian approach to derive the 3TC and LPV pharmacokinetic parameters on the basis of previously published pharmacokinetic models for HIV-infected children. We analyzed 114 LPV and 180 3TC plasma concentrations from 69 infants and 92 infants, respectively. A total of 30 LPV and 20 3TC observations were considered missing doses and discarded from the Bayesian analysis. The overall population analysis showed that 30 to 40% of the infants did not reach therapeutic targets, regardless of treatment group. The median LPV trough concentrations at weeks 6, 26, and 38 were 2.8 mg/liter (interquartile range [IQR], 1.7 to 4.4 mg/liter), 5.6 mg/liter (IQR, 3.2 to 7.7 mg/liter), and 3.4 mg/liter (IQR, 2.3 to 7.3 mg/ liter), respectively. The median 3TC area under the curve from 0 to 12 h after the last drug intake were 5.6 mg · h/liter (IQR, 4.1 to 7.8 mg · h/liter), 5.9 mg · h/liter (IQR, 5.1 to 7.5 mg · h/liter), and 7.3 mg · h/liter (IQR, 4.9 to 8.5 mg · h/liter) at weeks 6, 26, and 38, respectively. Use of the therapeutic doses recommended by the WHO would have resulted in a higher proportion of infants achieving the targets. However, no HIV-1 infection was reported among these infants. These results suggest that the prophylactic targets for both 3TC and LPV may be lower than the ther-

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The Pharmacokinetics and Acceptability of Lopinavir/Ritonavir Minitab Sprinkles, Tablets, and Syrups in African HIV-Infected Children

Abstract: LPV/r exposure from minitabs was comparable with syrup, but lower than tablets, with no significant differences in subtherapeutic concentrations. Minitabs were more acceptable than syrups for younger children, but older children preferred tablets.

Cited by 59 publications

References 8 publications

An update on the HIV treatment cascade in children and adolescents

An update on the HIV treatment cascade in children and adolescents

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children’s Acceptability of Oral Formulations (CALF) Study

Are Prophylactic and Therapeutic Target Concentrations Different?: the Case of Lopinavir-Ritonavir or Lamivudine Administered to Infants for Prevention of Mother-to-Child HIV-1 Transmission during Breastfeeding

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