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LitCovid-PubTator

2_test

{"project":"2_test","denotations":[{"id":"32389720-7558665-48149098","span":{"begin":368,"end":370},"obj":"7558665"},{"id":"32389720-12441132-48149099","span":{"begin":374,"end":376},"obj":"12441132"},{"id":"32389720-11499789-48149100","span":{"begin":380,"end":382},"obj":"11499789"},{"id":"32389720-8957238-48149101","span":{"begin":386,"end":388},"obj":"8957238"},{"id":"32389720-25155592-48149102","span":{"begin":454,"end":456},"obj":"25155592"},{"id":"32389720-25155592-48149103","span":{"begin":1105,"end":1107},"obj":"25155592"},{"id":"32389720-431047-48149104","span":{"begin":1111,"end":1113},"obj":"431047"},{"id":"32389720-12243724-48149105","span":{"begin":1117,"end":1119},"obj":"12243724"},{"id":"32389720-1030706-48149106","span":{"begin":1123,"end":1125},"obj":"1030706"},{"id":"32389720-20219329-48149107","span":{"begin":1655,"end":1657},"obj":"20219329"},{"id":"T35193","span":{"begin":368,"end":370},"obj":"7558665"},{"id":"T71814","span":{"begin":374,"end":376},"obj":"12441132"},{"id":"T86676","span":{"begin":380,"end":382},"obj":"11499789"},{"id":"T46347","span":{"begin":386,"end":388},"obj":"8957238"},{"id":"T79422","span":{"begin":454,"end":456},"obj":"25155592"},{"id":"T99834","span":{"begin":1105,"end":1107},"obj":"25155592"},{"id":"T30874","span":{"begin":1111,"end":1113},"obj":"431047"},{"id":"T42597","span":{"begin":1117,"end":1119},"obj":"12243724"},{"id":"T58158","span":{"begin":1123,"end":1125},"obj":"1030706"},{"id":"T92937","span":{"begin":1655,"end":1657},"obj":"20219329"}],"text":"4 Azithromycin\nWhen the same ion-trapping concepts are applied to azithromycin, the expected accumulation ratio in lysosomes compared with cytosol is calculated as 52 000-fold, which is very similar to that of hydroxychloroquine. After administration of azithromycin, a large fraction of the dose will reside in lysosomes where it also binds to acidic phospholipids [10], [11], [12], [13]. A clinical study supports azithromycin lysosomal accumulation [14]. In this study, the experimentally measured average total azithromycin concentrations in polymorphonuclear white blood cells (PMLs) was over 14 000 ng/mL. However, the model-predicted unionized azithromycin concentration of 6.0 ng/mL in the cytosol of PMLs was comparable to the measured interstitial concentrations in the muscle (8.7 ng/mL) and subcutis (4.1 ng/mL). Hence, the measured concentrations in white blood cells was approximately 2000-fold higher than the measured unbound concentrations in the interstitial space. Considering the lysosomal volume is estimated to range between 0.5 to 5% of the cellular volume depending on cell type [14], [15], [16], [17], these concentrations are consistent with the expected magnitude of lysosomal accumulation and explain these very high cellular concentrations.\nJust as for hydroxychloroquine, the pharmacokinetic parameters of azithromycin confirm these extreme distribution properties. The volume of distribution of azithromycin was reported to be 31 L/kg and the half-life was 68 h, despite a relatively rapid clearance of 630 mL/min [18]. Furthermore, the pharmacokinetics of azithromycin have been shown to be affected by the disease state [19]. In a preclinical investigation, azithromycin was injected into rats and interstitial concentrations were measured in both thighs using microdialysis. After 3 h, an infection was induced in only one leg. Shortly after, the unbound interstitial tissue concentrations increased in the infected leg, without any additional dosing. The results can be explained by macrophages loaded with lysosomal azithromycin migrating to and releasing drug at the infection site."}

LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T2","span":{"begin":571,"end":576},"obj":"Body_part"},{"id":"T3","span":{"begin":870,"end":875},"obj":"Body_part"},{"id":"T4","span":{"begin":1858,"end":1861},"obj":"Body_part"},{"id":"T5","span":{"begin":1890,"end":1909},"obj":"Body_part"},{"id":"T6","span":{"begin":1903,"end":1909},"obj":"Body_part"},{"id":"T7","span":{"begin":1951,"end":1954},"obj":"Body_part"}],"attributes":[{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A3","pred":"uberon_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/UBERON_0000978"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0005169"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/UBERON_0000978"}],"text":"4 Azithromycin\nWhen the same ion-trapping concepts are applied to azithromycin, the expected accumulation ratio in lysosomes compared with cytosol is calculated as 52 000-fold, which is very similar to that of hydroxychloroquine. After administration of azithromycin, a large fraction of the dose will reside in lysosomes where it also binds to acidic phospholipids [10], [11], [12], [13]. A clinical study supports azithromycin lysosomal accumulation [14]. In this study, the experimentally measured average total azithromycin concentrations in polymorphonuclear white blood cells (PMLs) was over 14 000 ng/mL. However, the model-predicted unionized azithromycin concentration of 6.0 ng/mL in the cytosol of PMLs was comparable to the measured interstitial concentrations in the muscle (8.7 ng/mL) and subcutis (4.1 ng/mL). Hence, the measured concentrations in white blood cells was approximately 2000-fold higher than the measured unbound concentrations in the interstitial space. Considering the lysosomal volume is estimated to range between 0.5 to 5% of the cellular volume depending on cell type [14], [15], [16], [17], these concentrations are consistent with the expected magnitude of lysosomal accumulation and explain these very high cellular concentrations.\nJust as for hydroxychloroquine, the pharmacokinetic parameters of azithromycin confirm these extreme distribution properties. The volume of distribution of azithromycin was reported to be 31 L/kg and the half-life was 68 h, despite a relatively rapid clearance of 630 mL/min [18]. Furthermore, the pharmacokinetics of azithromycin have been shown to be affected by the disease state [19]. In a preclinical investigation, azithromycin was injected into rats and interstitial concentrations were measured in both thighs using microdialysis. After 3 h, an infection was induced in only one leg. Shortly after, the unbound interstitial tissue concentrations increased in the infected leg, without any additional dosing. The results can be explained by macrophages loaded with lysosomal azithromycin migrating to and releasing drug at the infection site."}

LitCovid-PD-MONDO

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T7","span":{"begin":804,"end":812},"obj":"Disease"},{"id":"T8","span":{"begin":1824,"end":1833},"obj":"Disease"},{"id":"T9","span":{"begin":2105,"end":2114},"obj":"Disease"}],"attributes":[{"id":"A7","pred":"mondo_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MONDO_0006591"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/MONDO_0005550"}],"text":"4 Azithromycin\nWhen the same ion-trapping concepts are applied to azithromycin, the expected accumulation ratio in lysosomes compared with cytosol is calculated as 52 000-fold, which is very similar to that of hydroxychloroquine. After administration of azithromycin, a large fraction of the dose will reside in lysosomes where it also binds to acidic phospholipids [10], [11], [12], [13]. A clinical study supports azithromycin lysosomal accumulation [14]. In this study, the experimentally measured average total azithromycin concentrations in polymorphonuclear white blood cells (PMLs) was over 14 000 ng/mL. However, the model-predicted unionized azithromycin concentration of 6.0 ng/mL in the cytosol of PMLs was comparable to the measured interstitial concentrations in the muscle (8.7 ng/mL) and subcutis (4.1 ng/mL). Hence, the measured concentrations in white blood cells was approximately 2000-fold higher than the measured unbound concentrations in the interstitial space. Considering the lysosomal volume is estimated to range between 0.5 to 5% of the cellular volume depending on cell type [14], [15], [16], [17], these concentrations are consistent with the expected magnitude of lysosomal accumulation and explain these very high cellular concentrations.\nJust as for hydroxychloroquine, the pharmacokinetic parameters of azithromycin confirm these extreme distribution properties. The volume of distribution of azithromycin was reported to be 31 L/kg and the half-life was 68 h, despite a relatively rapid clearance of 630 mL/min [18]. Furthermore, the pharmacokinetics of azithromycin have been shown to be affected by the disease state [19]. In a preclinical investigation, azithromycin was injected into rats and interstitial concentrations were measured in both thighs using microdialysis. After 3 h, an infection was induced in only one leg. Shortly after, the unbound interstitial tissue concentrations increased in the infected leg, without any additional dosing. The results can be explained by macrophages loaded with lysosomal azithromycin migrating to and releasing drug at the infection site."}

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T61","span":{"begin":0,"end":15},"obj":"Sentence"},{"id":"T62","span":{"begin":16,"end":230},"obj":"Sentence"},{"id":"T63","span":{"begin":231,"end":390},"obj":"Sentence"},{"id":"T64","span":{"begin":391,"end":458},"obj":"Sentence"},{"id":"T65","span":{"begin":459,"end":612},"obj":"Sentence"},{"id":"T66","span":{"begin":613,"end":825},"obj":"Sentence"},{"id":"T67","span":{"begin":826,"end":984},"obj":"Sentence"},{"id":"T68","span":{"begin":985,"end":1270},"obj":"Sentence"},{"id":"T69","span":{"begin":1271,"end":1396},"obj":"Sentence"},{"id":"T70","span":{"begin":1397,"end":1551},"obj":"Sentence"},{"id":"T71","span":{"begin":1552,"end":1659},"obj":"Sentence"},{"id":"T72","span":{"begin":1660,"end":1809},"obj":"Sentence"},{"id":"T73","span":{"begin":1810,"end":1862},"obj":"Sentence"},{"id":"T74","span":{"begin":1863,"end":1986},"obj":"Sentence"},{"id":"T75","span":{"begin":1987,"end":2120},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"4 Azithromycin\nWhen the same ion-trapping concepts are applied to azithromycin, the expected accumulation ratio in lysosomes compared with cytosol is calculated as 52 000-fold, which is very similar to that of hydroxychloroquine. After administration of azithromycin, a large fraction of the dose will reside in lysosomes where it also binds to acidic phospholipids [10], [11], [12], [13]. A clinical study supports azithromycin lysosomal accumulation [14]. In this study, the experimentally measured average total azithromycin concentrations in polymorphonuclear white blood cells (PMLs) was over 14 000 ng/mL. However, the model-predicted unionized azithromycin concentration of 6.0 ng/mL in the cytosol of PMLs was comparable to the measured interstitial concentrations in the muscle (8.7 ng/mL) and subcutis (4.1 ng/mL). Hence, the measured concentrations in white blood cells was approximately 2000-fold higher than the measured unbound concentrations in the interstitial space. Considering the lysosomal volume is estimated to range between 0.5 to 5% of the cellular volume depending on cell type [14], [15], [16], [17], these concentrations are consistent with the expected magnitude of lysosomal accumulation and explain these very high cellular concentrations.\nJust as for hydroxychloroquine, the pharmacokinetic parameters of azithromycin confirm these extreme distribution properties. The volume of distribution of azithromycin was reported to be 31 L/kg and the half-life was 68 h, despite a relatively rapid clearance of 630 mL/min [18]. Furthermore, the pharmacokinetics of azithromycin have been shown to be affected by the disease state [19]. In a preclinical investigation, azithromycin was injected into rats and interstitial concentrations were measured in both thighs using microdialysis. After 3 h, an infection was induced in only one leg. Shortly after, the unbound interstitial tissue concentrations increased in the infected leg, without any additional dosing. The results can be explained by macrophages loaded with lysosomal azithromycin migrating to and releasing drug at the infection site."}

PMC:7204663 / 7575-9695 JSONTXT

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PMC:7204663 / 7575-9695 JSON TXT