Table 2.
Overview of clinical pharmacokinetic studies in neglected tropical diseases
| Disease | Study | Drug | Administration route | Analytes (parent and metabolites) | Analyzed matrix | Subjects (n) | Pediatrics included | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Chagas disease | |||||||||||
| Shapiro et al. [21] | Allopurinol riboside | Oral | Allopurinol (riboside), oxipurinol | Plasma, urine | Male healthy subjects (32) | ||||||
| Were et al. [22] | Allopurinol riboside | Oral | Allopurinol riboside, oxipurinol | Plasma, urine | Male healthy subjects (3) | ||||||
| Garcia-Bournissen et al. [23] | Nifurtimox | Oral | Nifurtimox | Plasma | Healthy subjects (7) | ||||||
| Richle et al. [24] | Benznidazole | Oral | Benznidazole | Plasma | Chagas disease patients (8) | ||||||
| Altcheh et al. [25] | Benznidazole | Oral | Benznidazole | Plasma | Chagas disease patients (40) | ✓ | |||||
| Soy et al. [26] | Benznidazole | Oral | Benznidazole | Plasma | Chagas disease patients (39) | ||||||
| Human African trypanosomiasis | |||||||||||
| Bronner et al. [28] | Pentamidine | IM | Pentamidine | Plasma, whole blood, CSF | T. b. gambiense trypanosomiasis patients (11) | ||||||
| Bronner et al. [29] | Pentamidine | IV | Pentamidine | Plasma | T. b. gambiense trypanosomiasis patients (11) | ||||||
| Harrison et al. [30] | Melarsoprol | IV | Arsenic | Urine | T. b. rhodesiense trypanosomiasis patients (28) | ||||||
| Burri et al. [31] | Melarsoprol | IV | Melarsoprol | Serum, CSF | T. b. gambiense trypanosomiasis patients (19) | ||||||
| Burri et al. [32] | Melarsoprol | IV | Melarsoprol | Serum, CSF | T. b. gambiense trypanosomiasis patients (22) | ||||||
| Bronner et al. [33] | Melarsoprol | IV | Melarsoprol | Plasma, urine, CSF | T. b. gambiense trypanosomiasis patients (8) | ||||||
| Milord et al. [34] | Eflornithine | IV | Eflornithine | Serum, CSF | T. b. gambiense trypanosomiasis patients (63) | ✓ | |||||
| Na-Bangchang et al. [35] | Eflornithine | Oral | Eflornithine | Plasma, CSF | T. b. gambiense trypanosomiasis patients (25) | ||||||
| Jansson-Lofmark et al. [36] | Eflornithine | Oral | Eflornithine | Plasma, CSF | T. b. gambiense trypanosomiasis patients (25) | ||||||
| Tarral et al. [37], Gualano et al. [38] | Fexinidazole | Oral | Fexinidazole sulfoxide, fexinidazole sulfone | Plasma, urine | Male healthy subjects (154) | ||||||
| Leishmaniasis | |||||||||||
| Al Jaser et al. [44] | Sodium stibogluconate | IM | Antimony | Blood, urine | CL patients (29) | ||||||
| Al Jaser et al. [52] | Sodium stibogluconate | IM | Antimony | Blood, skin biopsies | CL patients (9) | ||||||
| Reymond et al. [47] | Sodium stibogluconate | IV | Antimony | Serum | Patient with AIDS and VL (1) | ||||||
| Vasquez et al. [45] | Pentavalent antimony | IM | Pentavalent and trivalent antimony | Blood, urine | Healthy subjects (5) | ||||||
| Chulay et al. [48] | Sodium stibogluconate, meglumine antimoniate | IM | Antimony | Blood | VL patients (5) | ||||||
| Cruz et al. [53] | Meglumine antimoniate | IM | Antimony | Plasma, urine | CL patient (24) | ✓ | |||||
| Zaghloul et al. [46] | Sodium stibogluconate | IM | Antimony | Plasma, urine | CL patient (12) | ||||||
| Shapiro et al. [21] | Allopurinol riboside | Oral | Allopurinol, riboside, oxipurinol | Plasma, urine | Male healthy subjects (32) | ||||||
| Were and Shapiro [22] | Allopurinol riboside | Oral | Allopurinol riboside, oxipurinol | Plasma, urine | Male healthy subjects (3) | ||||||
| Musa et al. [49] | Paromomycin sulphate | IM | Paromomycin | Plasma, urine | VL patients (9) | ✓ | |||||
| Ravis et al. [50] | Paramomycin, WR 279396 | Topical | Paromomycin | Plasma | CL patients (60) | ✓ | |||||
| Sundar et al. [51] | Sitamaquine | Oral | Sitamaquine, desethyl-sitamaquine | Plasma | VL patients (41) | ||||||
| Dorlo et al. [40] | Miltefosine | Oral | Miltefosine | Plasma | Old world CL patients (31) | ||||||
| Dorlo et al. [41] | Miltefosine | Oral | Miltefosine | Plasma | VL patients (96) | ✓ | |||||
| Dorlo et al. [42] | Miltefosine | Oral | Miltefosine | Plasma | Simulated female VL patients | ||||||
| Dorlo et al. [43] | Miltefosine | Oral | Miltefosine | Plasma | VL patients (81) | ✓ | |||||
| Buruli ulcer | |||||||||||
| Alffenaar et al. [55] | Streptomycin-rifampicin, rifampin-clarithromycin | Oral | Rifampicin, 25-desacetylrifampicin, clarithromycin, 14OH-clarithromycin | Plasma | Buruli ulcer patients (13) | ✓ | |||||
| Leprosy | |||||||||||
| Mehta et al. [63] | Rifampicin | Oral | Rifampicin | Serum | MB (6) and PB (12) leprosy patients | ||||||
| Venkatesan et al. [61] | Rifampicin and dapsone | Oral | Rifampicin and dapsone | Plasma, urine | Leprosy patients (15) | ||||||
| Pieters and Zuidema [56] | Monoacetyldapsone | IA | Dapsone | Serum | Healthy subjects (22) | ||||||
| Pieters and Zuidema [57] | Dapsone | Oral | Dapsone | Serum | Healthy subjects (5) | ||||||
| Garg et al. [58] | Dapsone | Oral | Dapsone, monoacetyldapsone | Plasma | Lepromatous leprosy patients (15) | ||||||
| Venkatesan et al. [62] | Dapsomine | Oral | Dapsone | Plasma | Lepromatous leprosy patients(14) | ||||||
| Pieters et al. [64] | Dapsone | Oral | Dapsone | Plasma | Leprosy patients (23) | ||||||
| Moura et al. [59] | Dapsone | Oral | Dapsone | Plasma | MB leprosy patients (33) | ||||||
| Nix et al. [60] | Clofazamine | Oral | Clofazamine | Plasma | Healthy subjects (16) | ||||||
| Teo et al. [66] | Thalidomide | Oral | Thalidomide | Plasma | Healthy subjects (17) | ||||||
| Teo et al. [65] | Thalidomide | Oral | Thalidomide | Plasma | Healthy subjects (15) | ||||||
| Trachoma | |||||||||||
| Amsden et al. [67] | Azithromycin, albendazole, ivermectin | Oral | Azithromycin, albendazole sulfoxide, ivermectin H2B1a and H2B1b | Plasma | Healthy subjects (18) | ||||||
| El-Tahtawy et al. [68] | Ivermectin | Oral | Ivermectin H2B1a and H2B1b | Plasma | Healthy subjects (15) | ||||||
| Cysticercosis/taeniasis | |||||||||||
| Jung et al. [75] | Albendazole | Oral | Albendazole sulfoxide | Plasma | Brain cysticercosis patients (8) | ||||||
| Sanchez et al. [70] | Albendazole | Oral | Albendazole sulfoxide | Plasma, urine | Parenchymal brain cysticercosis patients (10) | ||||||
| Jung et al. [69] | Albendazole | Oral | Albendazole sulfoxide | Plasma | Brain cysticercosis patients (8) | ✓ | |||||
| Takayanagui et al. [71] | Albendazole | Oral | Albendazole sulfoxide | Plasma | Parenchymal brain cysticercosis patients (24) | ||||||
| Na-Bangchang et al. [72] | Praziquantel | Oral | Praziquantel | Plasma | Neurocysticercosis patients (11) | ||||||
| Jung et al. [73] | Praziquantel | Oral | Praziquantel | Plasma | Healthy subjects (8) | ||||||
| Garcia et al. [74] | Praziquantel, albendazole | Oral | Praziquantel, albendazole sulfoxide | Plasma | Neurocysticercosis patients (32) | ||||||
| Echinococcosis | |||||||||||
| Cotting et al. [76] | Albendazole | Oral | Albendazole sulfoxide | Plasma | Echinococcosis patients (19) | ||||||
| Mingjie et al. [77] | Albendazole | Oral | Albendazole sulfoxide | Serum | Male cystic echinococcosis patients (7) | ||||||
| Schipper et al. [78] | Albendazole | Oral | Albendazole sulfoxide | Plasma | Male healthy subjects (6) | ||||||
| Food-borne trematodiases | |||||||||||
| Na Bangchang et al. [79] | Praziquantel | Oral | Praziquantel | ? | Opisthorchiasis patients (18) | ||||||
| Choi et al. [80] | Praziquantel | Oral | Praziquantel | Plasma | Healthy subjects (12) and clonorchiasis patients (20) | ||||||
| Lecaillon et al. [81] | Triclabendazole | Oral | Triclabendazole, sulfoxide, sulfone | Plasma | Fascioliasis patients (20) | ||||||
| El-Tantawy et al. [82] | Triclabendazole | Oral | Triclabendazole sulfoxide | Plasma | Healthy subjects (12) and fascioliasis patients (12) | ||||||
| Lymphatic filariasis | |||||||||||
| Shenoy et al. [83] | Diethylcarbamazine, albendazole | Oral | Diethylcarbamazine, albendazole sulfoxide | Plasma | Healthy subjects (42) | ||||||
| Sarin et al. [84] | Albendazole sulfoxide | Oral | Albendazole sulfoxide, albendazole sulfone | Plasma | Healthy subjects (10) | ||||||
| Abdel-tawab et al. [85] | Albendazole | Oral | Albendazole, sulfoxide, albendazole sulfone | Serum, breast milk | Lactating women (33) | ||||||
| Onchocerciasis | |||||||||||
| Lecaillon et al. [93] | Amocarzine | Oral | Amocarzine, N-oxide metabolite | Plasma, urine | Onchocerciasis patients (41) | ||||||
| Lecaillon et al. [94] | Amocarzine | Oral | Amocarzine, N-oxide metabolite | Plasma, urine | Male onchocerciasis patients (20) | ||||||
| Awadzi et al. [86] | Albendazole | Oral | Albendazole sulfoxide | Plasma | Onchocerciasis patients (36) | ||||||
| Awadzi et al. [87] | Ivermectin, albendazole | Oral | Ivermectin, albendazole sulfoxide | Plasma | Male onchocerciasis patients (42) | ||||||
| Okonkwo et al. [88] | Ivermectin | Oral | Ivermectin | Plasma, urine, saliva | Onchocerciasis patients (9) | ||||||
| Baraka et al. [89] | Ivermectin | Oral | Ivermectin | Plasma, tissues | Onchocerciasis patients (25), healthy subjects (14) | ||||||
| Homeida et al. [90] | Ivermectin | Oral | Ivermectin | Plasma | Male subjects (10) | ||||||
| Chijioke et al. [91] | Suramin | IV | Suramin | Plasma | Male onchocerciasis patients (10) | ||||||
| Korth-Bradley et al. [92] | Moxidectin | Oral | Moxidectin | Plasma, breast milk | Healthy lactating women (12) | ||||||
| Schistosomiasis | |||||||||||
| Nordgren et al. [98] | Metrifonate | Oral | Metrifonate, dichlorvos | Plasma | Male schistosomiasis patients (2) | ||||||
| Daneshmend and Homeida [99] | Oxamniquine | Oral | Oxamniquine | Plasma | Hepatosplenic schistosomiasis patients (9), healthy subjects (5) | ||||||
| Pehrson et al. [95] | Praziquantel | Oral | Praziquantel | Serum, urine, dialysis fluid | Patient with uremia (1) | ||||||
| Mandour et al. [96] | Praziquantel | Oral | Praziquantel | Serum or plasma | Healthy subjects (20), schistosomiasis patients (9) | ||||||
| Valencia et al. [97] | Praziquantel | Oral | Praziquantel | Serum | Schistosoma japonicum patients (4) | ||||||
| El Guiniady et al. [16] | Praziquantel | Oral | Praziquantel | Serum | Schistosoma mansoni patients (40) | ||||||
| Rabies | |||||||||||
| Merigan et al. [100] | Human leukocyte interferon | I-VENTRIC, IT, IM | Human leukocyte interferon | Serum, CSF | Suspected rabies patients (2), symptomatic rabies patients (5) | ||||||
| Lang et al. [17] | Equine rabies immunoglobulin | IM | Anti-rabies antibodies | Serum | Healthy subjects (27) | ||||||
| Gogtay et al. [18] | IgG1 monoclonal antibody | IM | Anti-rabies antibodies | Serum | Male healthy subjects (29) | ||||||
| Disease | Study | Analysis method | Aim of the study | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Comparing concentrations (1) | Noncompartmental (2) | Compartmental (individual-based) (3) | Compartmental (population-based) (4) | Simulation and/or extrapolation (5) | Descriptive | Suggesting alternative dose regimens | Comparing different formulations | Evaluating drug–drug and food interactions | Evaluating exposure-response relationships | ||
| Chagas disease | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Shapiro et al. [21] | ✓ | ✓ | |||||||||
| Were et al. [22] | ✓ | ✓ | |||||||||
| Garcia-Bournissen et al. [23] | ✓ | ✓ | ✓ | ||||||||
| Richle et al. [24] | ✓ | ✓ | |||||||||
| Altcheh et al. [25] | ✓ | ✓ | ✓ | ||||||||
| Soy et al. [26] | ✓ | ✓ | ✓ | ||||||||
| Human African trypanosomiasis | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Bronner et al. [28] | ✓ | ✓ | |||||||||
| Bronner et al. [29] | ✓ | ✓ | |||||||||
| Harrison et al. [30] | ✓ | ✓ | |||||||||
| Burri et al. [31] | ✓ | ✓ | ✓ | ||||||||
| Burri et al. [32] | ✓ | ✓ | |||||||||
| Bronner et al. [33] | ✓ | ✓ | |||||||||
| Milord et al. [34] | ✓ | ✓ | |||||||||
| Na-Bangchang et al. [35] | ✓ | ✓ | ✓ | ||||||||
| Jansson-Lofmark et al. [36] | ✓ | ✓ | |||||||||
| Tarral et al. [37], Gualano et al. [38] | ✓ | ✓ | ✓ | ✓ | ✓ | ||||||
| Leishmaniasis | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Al Jaser et al. [44] | ✓ | ✓ | |||||||||
| Al Jaser et al. [52] | ✓ | ✓ | |||||||||
| Reymond et al. [47] | ✓ | ✓ | |||||||||
| Vasquez et al. [45] | ✓ | ✓ | |||||||||
| Chulay et al. [48] | ✓ | ✓ | |||||||||
| Cruz et al. [53] | ✓ | ✓ | |||||||||
| Zaghloul et al. [46] | ✓ | ✓ | ✓ | ||||||||
| Shapiro et al. [21] | ✓ | ✓ | |||||||||
| Were and Shapiro [22] | ✓ | ✓ | |||||||||
| Musa et al. [49] | ✓ | ✓ | |||||||||
| Ravis et al. [50] | ✓ | ✓ | |||||||||
| Sundar et al. [51] | ✓ | ✓ | |||||||||
| Dorlo et al. [40] | ✓ | ✓ | |||||||||
| Dorlo et al. [41] | ✓ | ✓ | ✓ | ||||||||
| Dorlo et al. [42] | ✓ | ✓ | ✓ | ||||||||
| Dorlo et al. [43] | ✓ | ✓ | |||||||||
| Buruli ulcer | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Alffenaar et al. [55] | ✓ | ✓ | |||||||||
| Leprosy | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Mehta et al. [63] | ✓ | ✓ | |||||||||
| Venkatesan et al. [61] | ✓ | ✓ | |||||||||
| Pieters and Zuidema [56] | ✓ | ✓ | ✓ | ||||||||
| Pieters and Zuidema [57] | ✓ | ✓ | |||||||||
| Garg et al. [58] | ✓ | ✓ | |||||||||
| Venkatesan et al. [62] | ✓ | ✓ | |||||||||
| Pieters et al. [64] | ✓ | ✓ | |||||||||
| Moura et al. [59] | ✓ | ✓ | |||||||||
| Nix et al. [60] | ✓ | ✓ | ✓ | ||||||||
| Teo et al. [66] | ✓ | ✓ | ✓ | ||||||||
| Teo et al. [65] | ✓ | ✓ | |||||||||
| Trachoma | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Amsden et al. [67] | ✓ | ✓ | |||||||||
| El-Tahtawy et al. [68] | ✓ | ✓ | ✓ | ||||||||
| Cysticercosis/taeniasis | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Jung et al. [75] | ✓ | ✓ | |||||||||
| Sanchez et al. [70] | ✓ | ✓ | |||||||||
| Jung et al. [69] | ✓ | ✓ | |||||||||
| Takayanagui et al. [71] | ✓ | ✓ | |||||||||
| Na-Bangchang et al. [72] | ✓ | ✓ | |||||||||
| Jung et al. [73] | ✓ | ✓ | |||||||||
| Garcia et al. [74] | ✓ | ✓ | |||||||||
| Echinococcosis | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Cotting et al. [76] | ✓ | ✓ | |||||||||
| Mingjie et al. [77] | ✓ | ✓ | |||||||||
| Schipper et al. [78] | ✓ | ✓ | |||||||||
| Food-borne trematodiases | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Na Bangchang et al. [79] | ✓ | ✓ | |||||||||
| Choi et al. [80] | ✓ | ✓ | |||||||||
| Lecaillon et al. [81] | ✓ | ✓ | |||||||||
| El-Tantawy et al. [82] | ✓ | ✓ | |||||||||
| Lymphatic filariasis | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Shenoy et al. [83] | ✓ | ✓ | |||||||||
| Sarin et al. [84] | ✓ | ✓ | |||||||||
| Abdel-tawab et al. [85] | ✓ | ✓ | |||||||||
| Onchocerciasis | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Lecaillon et al. [93] | ✓ | ✓ | |||||||||
| Lecaillon et al. [94] | ✓ | ✓ | |||||||||
| Awadzi et al. [86] | ✓ | ✓ | |||||||||
| Awadzi et al. [87] | ✓ | ✓ | |||||||||
| Okonkwo et al. [88] | ✓ | ✓ | |||||||||
| Baraka et al. [89] | ✓ | ✓ | |||||||||
| Homeida et al. [90] | ✓ | ✓ | ✓ | ||||||||
| Chijioke et al. [91] | ✓ | ✓ | |||||||||
| Korth-Bradley et al. [92] | ✓ | ✓ | |||||||||
| Schistosomiasis | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Nordgren et al. [98] | ✓ | ✓ | |||||||||
| Daneshmend and Homeida [99] | ✓ | ✓ | |||||||||
| Pehrson et al. [95] | ✓ | ✓ | |||||||||
| Mandour et al. [96] | ✓ | ✓ | ✓ | ||||||||
| Valencia et al. [97] | ✓ | ✓ | |||||||||
| El Guiniady et al. [16] | ✓ | ✓ | |||||||||
| Rabies | 1 | 2 | 3 | 4 | 5 | a | b | c | d | e | |
| Merigan et al. [100] | ✓ | ✓ | |||||||||
| Lang et al. [17] | ✓ | ✓ | |||||||||
| Gogtay et al. [18] | ✓ | ✓ | |||||||||
AIDS acquired immune deficiency syndrome, CL cutaneous leishmaniasis, CSF cerebrospinal fluid, IgG1 immunoglobulin G1, IA intra-adipose, IM intramuscular, IT intrathecal, IV intravenous, I-VENTRIC intraventricular, MB multibacillary, PL paucibacillary, VL visceral leishmaniasis, ? unknown