TY - JOUR
T1 - Influence of Malnutrition on the Pharmacokinetics of Drugs Used in the Treatment of Poverty-Related Diseases
T2 - A Systematic Review
AU - Verrest, Luka
AU - Wilthagen, Erica A.
AU - Beijnen, Jos H.
AU - Huitema, Alwin D.R.
AU - Dorlo, Thomas P.C.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
PY - 2021/9
Y1 - 2021/9
N2 - Background: Patients affected by poverty-related infectious diseases (PRDs) are disproportionally affected by malnutrition. To optimize treatment of patients affected by PRDs, we aimed to assess the influence of malnutrition associated with PRDs on drug pharmacokinetics, by way of a systematic review. Methods: A systematic review was performed on the effects of malnourishment on the pharmacokinetics of drugs to treat PRDs, including HIV, tuberculosis, malaria, and neglected tropical diseases. Results: In 21/29 PRD drugs included in this review, pharmacokinetics were affected by malnutrition. Effects were heterogeneous, but trends were observed for specific classes of drugs and different types and degrees of malnutrition. Bioavailability of lumefantrine, sulfadoxine, pyrimethamine, lopinavir, and efavirenz was decreased in severely malnourished patients, but increased for the P-glycoprotein substrates abacavir, saquinavir, nevirapine, and ivermectin. Distribution volume was decreased for the lipophilic drugs isoniazid, chloroquine, and nevirapine, and the α1-acid glycoprotein-bound drugs quinine, rifabutin, and saquinavir. Distribution volume was increased for the hydrophilic drug streptomycin and the albumin-bound drugs rifampicin, lopinavir, and efavirenz. Drug elimination was decreased for isoniazid, chloroquine, quinine, zidovudine, saquinavir, and streptomycin, but increased for the albumin-bound drugs quinine, chloroquine, rifampicin, lopinavir, efavirenz, and ethambutol. Clinically relevant effects were mainly observed in severely malnourished and kwashiorkor patients. Conclusions: Malnutrition-related effects on pharmacokinetics potentially affect treatment response, particularly for severe malnutrition or kwashiorkor. However, pharmacokinetic knowledge is lacking for specific populations, especially patients with neglected tropical diseases and severe malnutrition. To optimize treatment in these neglected subpopulations, adequate pharmacokinetic studies are needed, including severely malnourished or kwashiorkor patients.
AB - Background: Patients affected by poverty-related infectious diseases (PRDs) are disproportionally affected by malnutrition. To optimize treatment of patients affected by PRDs, we aimed to assess the influence of malnutrition associated with PRDs on drug pharmacokinetics, by way of a systematic review. Methods: A systematic review was performed on the effects of malnourishment on the pharmacokinetics of drugs to treat PRDs, including HIV, tuberculosis, malaria, and neglected tropical diseases. Results: In 21/29 PRD drugs included in this review, pharmacokinetics were affected by malnutrition. Effects were heterogeneous, but trends were observed for specific classes of drugs and different types and degrees of malnutrition. Bioavailability of lumefantrine, sulfadoxine, pyrimethamine, lopinavir, and efavirenz was decreased in severely malnourished patients, but increased for the P-glycoprotein substrates abacavir, saquinavir, nevirapine, and ivermectin. Distribution volume was decreased for the lipophilic drugs isoniazid, chloroquine, and nevirapine, and the α1-acid glycoprotein-bound drugs quinine, rifabutin, and saquinavir. Distribution volume was increased for the hydrophilic drug streptomycin and the albumin-bound drugs rifampicin, lopinavir, and efavirenz. Drug elimination was decreased for isoniazid, chloroquine, quinine, zidovudine, saquinavir, and streptomycin, but increased for the albumin-bound drugs quinine, chloroquine, rifampicin, lopinavir, efavirenz, and ethambutol. Clinically relevant effects were mainly observed in severely malnourished and kwashiorkor patients. Conclusions: Malnutrition-related effects on pharmacokinetics potentially affect treatment response, particularly for severe malnutrition or kwashiorkor. However, pharmacokinetic knowledge is lacking for specific populations, especially patients with neglected tropical diseases and severe malnutrition. To optimize treatment in these neglected subpopulations, adequate pharmacokinetic studies are needed, including severely malnourished or kwashiorkor patients.
UR - http://www.scopus.com/inward/record.url?scp=85107285497&partnerID=8YFLogxK
U2 - 10.1007/s40262-021-01031-z
DO - 10.1007/s40262-021-01031-z
M3 - Review article
C2 - 34060020
AN - SCOPUS:85107285497
SN - 0312-5963
VL - 60
SP - 1149
EP - 1169
JO - Clinical Pharmacokinetics
JF - Clinical Pharmacokinetics
IS - 9
ER -