RESUMEN
Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic in late-phase development for uncomplicated urinary tract infection and uncomplicated urogenital gonorrhea. Two clinical studies were conducted to assess the pharmacokinetics (PK) and interethnic comparisons of oral gepotidacin (free-base and to-be-marketed mesylate formulations) administered as single doses ranging from 1500 to 3000 mg in fed and fasted states, and as 2 × 3000-mg doses given 12 hours apart under fed conditions in healthy participants of Japanese ancestry. Dose proportionality was observed in plasma exposures, and comparable area under the concentration-time curve (AUC) and maximum concentration were observed in fed and fasted states. Interethnic comparisons for Japanese versus non-Japanese participant data showed slightly higher plasma maximum concentration (7%-30%) yet similar plasma AUCs; slightly lower urine AUCs (11%-18%) were observed. The slightly higher plasma exposures in healthy Japanese versus White participants in the same study were attributed to lower mean body weights (64 kg versus ≈80 kg). Adverse events were primarily gastrointestinal, and when administered with food, gastrointestinal tolerability was improved. Overall, the gepotidacin PK and safety-risk profiles in healthy Japanese support potential evaluation of the global clinical doses in future studies.
Asunto(s)
Acenaftenos , Compuestos Heterocíclicos con 3 Anillos , Humanos , Voluntarios Sanos , Acenaftenos/farmacocinética , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Antibacterianos/farmacocinéticaRESUMEN
Gepotidacin is a novel, first-in-class triazaacenaphthylene antibiotic that may provide a new treatment option for antibiotic-resistant pathogens. Two pharmacokinetic evaluations of oral gepotidacin are presented: a relative bioavailability study that guided formulation development, followed by an adult and adolescent study of the final formulation. In the relative bioavailability study, after gepotidacin administration to 26 healthy adults as free-base roller-compacted (RC) tablets, free-base high-shear wet granulation (HSWG) tablets, and mesylate salt reference capsules, the RC tablet exposure ratios and 90% confidence intervals (CIs) were within the 0.80-to-1.25 confidence bounds; however, the HSWG tablet maximum observed concentration (Cmax) was higher than the reference (ratio, 1.15; 90% CI, 1.0113, 1.3047). In the healthy adult (n = 16) and adolescent (n = 17) study, a gepotidacin mesylate salt tablet was evaluated as a 1,500-mg single dose or 2 doses administered 6 or 12 h apart (6,000 mg total), or placebo was administered. The single-dose mean Cmax was â¼27% higher in adolescents than in adults, and area under the concentration-time curve (AUC) values were comparable in both populations. After 2 doses were administered, the mean Cmax values were similar for both age groups, and the mean AUC was â¼35% higher in adolescents than in adults. Concentrations increased proportionally with dose. Safety-risk profiles were similar for both age groups. Across studies, the most common adverse events were gastrointestinal. Overall, the pharmacokinetics of the final gepotidacin mesylate salt tablet have been well characterized, enrollment of adolescents into the pivotal trials is supported, and dosing intervals were determined that should provide adequate exposures for microbiological efficacy. (This study has been registered at ClinicalTrials.gov under identifiers NCT02853435 and NCT04079790.).
Asunto(s)
Acenaftenos , Inhibidores de Topoisomerasa , Acenaftenos/farmacocinética , Administración Oral , Adolescente , Adulto , Área Bajo la Curva , Disponibilidad Biológica , Estudios Cruzados , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Humanos , ComprimidosRESUMEN
BACKGROUND: With increasing concerns about the impact of frequent antibiotic usage on the human microbiome, it is important to characterize the potential for such effects in early antibiotic drug development clinical trials. In a randomised Phase 2a clinical trial study that evaluated the pharmacokinetics of repeated oral doses of gepotidacin, a first-in-chemical-class triazaacenaphthylene antibiotic with a distinct mechanism of action, in adult females with uncomplicated urinary tract infections for gepotidacin (GSK2140944) we evaluated the potential changes in microbiome composition across multiple time points and body-sites ( ClinicalTrials.gov : NCT03568942). RESULTS: Samples of gastrointestinal tract (GIT), pharyngeal cavity and vaginal microbiota were collected with consent from 22 patients at three time points relative to the gepotidacin dosing regimen; Day 1 (pre-dose), Day 5 (end of dosing) and Follow-up (Day 28 ± 3 days). Microbiota composition was determined by DNA sequencing of 16S rRNA gene variable region 4 amplicons. By Day 5, significant changes were observed in the microbiome diversity relative to pre-dose across the tested body-sites. However, by the Follow-up visit, microbiome diversity changes were reverted to compositions comparable to Day 1. The greatest range of microbiome changes by body-site were GIT followed by the pharyngeal cavity then vagina. In Follow-up visit samples we found no statistically significant occurrences of pathogenic taxa. CONCLUSION: Our findings suggest that gepotidacin alteration of the human microbiome after 5 days of dosing is temporary and rebound to pre-dosing states is evident within the first month post-treatment. We recommend that future antibiotic drug trials include similar exploratory investigations into the duration and context of microbiome modification and recovery. TRIAL REGISTRATION: NCT03568942 . Registered 26 June 2018.
Asunto(s)
Acenaftenos/administración & dosificación , Antibacterianos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Microbiota/efectos de los fármacos , Infecciones Urinarias/tratamiento farmacológico , Acenaftenos/farmacocinética , Adulto , Antibacterianos/farmacocinética , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Biodiversidad , Femenino , Tracto Gastrointestinal/microbiología , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Humanos , Persona de Mediana Edad , Faringe/microbiología , Infecciones Urinarias/microbiología , Vagina/microbiologíaRESUMEN
Triciribine (TCN) is a tricyclic nucleoside analog of adenosine and an inhibitor of Akt kinase. Triciribine 5'-monophosphate (TCNP) is a water-soluble analog of Triciribine and has progressed to Phase I and II clinical trials in oncology. TCNP is also an endogenous anabolite of TCN similar to other nucleoside phosphates. Clinical development of TCNP has been hampered by high pharmacokinetic variability due to complex interplay of TCN-TCNP conversion and reconversion in plasma, erythrocytes (RBC) and peripheral organs. TCN has been demonstrated to be an efficacious agent in mice models of acute lung injury at low doses (0.5 mg/kg/day) although its pharmacokinetic-pharmacodynamic (PK/PD) relationship remained unclear. We have developed and validated a sensitive, specific and robust LC/MS/MS assay for quantitation of TCN and TCNP in plasma and RBC. Using a simple protein precipitation method, quantitation of these analytes was accomplished with recoveries exceeding 85% and with a run time of 4 min. This assay was used to determine the pharmacokinetic parameters of TCN and TCNP in mice after single dose intravenous administration at 1, 3 and 10 mg/kg. TCNP accumulates in RBC, has low clearance and a half-life of 18 to 23 h. Unlike other nucleoside phosphates, TCNP was found to be relatively stable in mice plasma serving as a secondary depot. TCN levels were low and with high clearance relative to hepatic blood flow. A combination of sustained levels of TCNP in RBC and plasma serves as a depot for TCN to elicit robust therapeutic activity in acute lung injury mice models.
Asunto(s)
Acenaftenos/sangre , Cromatografía Liquida/métodos , Ribonucleósidos/sangre , Ribonucleótidos/sangre , Espectrometría de Masas en Tándem/métodos , Acenaftenos/farmacocinética , Animales , Eritrocitos/metabolismo , Modelos Lineales , Masculino , Ratones , Ratones Endogámicos C57BL , Reproducibilidad de los Resultados , Ribonucleósidos/farmacocinética , Ribonucleótidos/farmacocinética , Sensibilidad y EspecificidadRESUMEN
Gepotidacin is a novel triazaacenaphthylene bacterial topoisomerase inhibitor. This phase 1 nonrandomized, open-label, multicenter, 2-part study evaluated the pharmacokinetics, safety, and tolerability of oral gepotidacin 1500 mg in 3 different hepatic settings (normal, moderate impairment, and severe impairment). Gepotidacin was safe and generally tolerated in all subjects. Compared to subjects with normal hepatic function, gepotidacin plasma area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞ ) and maximum concentration significantly increased by 1.7- and 1.9-fold, respectively, in severe hepatic impairment; increases in moderate impairment were not statistically significant. No significant effect was observed for gepotidacin plasma elimination half-life (geometric mean range, 8.2-9.1 hours) across hepatic groups. Renal clearance increased in moderate (16%) and severe (52%) hepatic impairment vs normal. The mean fraction of gepotidacin dose excreted in urine increased with increasing hepatic impairment (normal, 7.5%; moderate, 11.2%; and severe, 19.9%). Urine gepotidacin concentrations remained high for 12 hours in all hepatic groups after dosing. Saliva gepotidacin concentrations displayed a linear relationship with plasma concentrations (R2 = 0.76). The ratio of saliva AUC to unbound plasma AUC and elimination half-life were not affected by hepatic impairment. These data indicate that gepotidacin dose adjustment is not required in mild to moderate hepatic impairment; severe hepatic impairment may require increases in dosing interval or dose reduction.
Asunto(s)
Acenaftenos/administración & dosificación , Antibacterianos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Hepatopatías/fisiopatología , Acenaftenos/efectos adversos , Acenaftenos/farmacocinética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/efectos adversos , Antibacterianos/farmacocinética , Área Bajo la Curva , Femenino , Semivida , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Gepotidacin is a novel triazaacenaphthylene bacterial topoisomerase inhibitor. In this phase 1, nonrandomized, open-label, parallel-group, multicenter, multipart study, the pharmacokinetics, safety, and tolerability of a single intravenous (IV) dose of gepotidacin 750 mg over 2 hours were evaluated in subjects with normal renal function, in those with moderate and severe renal impairment, and in end-stage renal disease (ESRD) on and not on dialysis. Administration of IV gepotidacin 750 mg was safe and generally tolerated in the study subjects. Dosing in severe renal impairment with and without hemodialysis resulted in significant increases in plasma drug levels and decreases in clearance. The geometric mean elimination half-life (t½ ) was minimally impacted (range 9.45 to 11.5 hours) in all the renal-impairment groups relative to normal renal function. Regardless of renal function, urine gepotidacin concentrations remained considerably high over a 12-hour period. Saliva concentrations displayed a linear relationship with plasma concentrations. The t½ in saliva was not impacted in the moderate-impairment and ESRD subjects and was comparable to t½ in plasma. Over a 4-hour dialysis, approximately 6% of the gepotidacin dose was removed. Overall, subjects with severe renal impairment and ESRD with and without hemodialysis may require adjustment in dose or dosing frequency.
Asunto(s)
Acenaftenos/farmacocinética , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Fallo Renal Crónico/metabolismo , Insuficiencia Renal/metabolismo , Inhibidores de Topoisomerasa/farmacocinética , Acenaftenos/administración & dosificación , Acenaftenos/sangre , Administración Intravenosa , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/sangre , Humanos , Fallo Renal Crónico/tratamiento farmacológico , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados no Aleatorios como Asunto/métodos , Farmacocinética , Insuficiencia Renal/tratamiento farmacológico , Insuficiencia Renal/fisiopatología , Seguridad , Saliva/metabolismo , Inhibidores de Topoisomerasa/administración & dosificación , Inhibidores de Topoisomerasa/sangreRESUMEN
We evaluated microbiological correlates for the successful treatment of Neisseria gonorrhoeae isolates from a phase 2 study of gepotidacin, a novel triazaacenaphthylene antibacterial, for therapy of uncomplicated urogenital gonorrhea. Culture, susceptibility testing, genotypic characterization, and frequency of resistance (FoR) were performed for selected isolates. Microbiological success was defined as culture-confirmed eradication of N. gonorrhoeae Against 69 baseline urogenital isolates, gepotidacin MICs ranged from ≤0.06 to 1 µg/ml (MIC90 = 0.5 µg/ml). For gepotidacin, the ratio of the area under the free-drug concentration-time curve to the MIC (fAUC/MIC) was associated with therapeutic success. Success was 100% (61/61) at fAUC/MICs of ≥48 and decreased to 63% (5/8) for fAUC/MICs of ≤25. All 3 isolates from microbiological failures were ciprofloxacin resistant, had a baseline gepotidacin MIC of 1 µg/ml, and carried a preexisting ParC D86N mutation, a critical residue for gepotidacin binding. In a test-of-cure analysis, the resistance to gepotidacin emerged in 2 isolates (MICs increased ≥32-fold) with additional GyrA A92T mutations, also implicated in gepotidacin binding. Test-of-cure isolates had the same sequence type as the corresponding baseline isolates. For 5 selected baseline isolates, all carrying a ParC D86N mutation, the in vitro FoR to gepotidacin was low (10-9 to 10-10); the resistant mutants had the same A92T mutation as the 2 isolates in which resistance emerged. Five participants with isolates harboring the ParC D86N mutation were treatment successes. In summary, fAUC/MICs of ≥48 predicted 100% microbiological success, including 3 isolates with the ParC D86N mutation (fAUC/MICs ≥ 97). Pharmacokinetic/pharmacodynamic determinations may help to evaluate new therapies for gonorrhea; further study of gepotidacin is warranted. (This study has been registered at ClinicalTrials.gov under identifier NCT02294682.).
Asunto(s)
Acenaftenos/farmacocinética , Antibacterianos/farmacocinética , Topoisomerasa de ADN IV/genética , Farmacorresistencia Bacteriana/genética , Gonorrea/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Neisseria gonorrhoeae/efectos de los fármacos , Acenaftenos/sangre , Acenaftenos/farmacología , Administración Oral , Adulto , Antibacterianos/sangre , Antibacterianos/farmacología , Área Bajo la Curva , Técnicas de Tipificación Bacteriana , Cultivo de Sangre , Ciprofloxacina/uso terapéutico , Topoisomerasa de ADN IV/metabolismo , Esquema de Medicación , Femenino , Expresión Génica , Gonorrea/sangre , Gonorrea/microbiología , Gonorrea/patología , Compuestos Heterocíclicos con 3 Anillos/sangre , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Mutación , Neisseria gonorrhoeae/enzimología , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/aislamiento & purificación , Resultado del TratamientoRESUMEN
Gepotidacin (GSK2140944), a novel triazaacenaphthylene bacterial topoisomerase inhibitor, is currently in clinical development for the treatment of bacterial infections. This study examined in vitro its activity against intracellular Staphylococcus aureus (involved in the persistent character of skin and skin structure infections) by use of a pharmacodynamic model and in relation to cellular pharmacokinetics in phagocytic cells. Compared to oxacillin, vancomycin, linezolid, daptomycin, azithromycin, and moxifloxacin, gepotidacin was (i) more potent intracellularly (the apparent bacteriostatic concentration [Cs ] was reached at an extracellular concentration about 0.7× its MIC and was not affected by mechanisms of resistance to the comparators) and (ii) caused a maximal reduction of the intracellular burden (maximum effect) of about -1.6 log10 CFU (which was better than that caused by linezolid, macrolides, and daptomycin and similar to that caused by moxifloxacin). After 24 h of incubation of infected cells with antibiotics at 100× their MIC, the intracellular persisting fraction was <0.1% with moxifloxacin, 0.5% with gepotidacin, and >1% with the other drugs. The accumulation and efflux of gepotidacin in phagocytes were very fast (kin and kout, â¼0.3 min-1; the plateau was reached within 15 min) but modest (intracellular concentration-to-extracellular concentration ratio, â¼1.6). In cell fractionation studies, about 40 to 60% of the drug was recovered in the soluble fraction and â¼40% was associated with lysosomes in uninfected cells. In infected cells, about 20% of cell-associated gepotidacin was recovered in a sedimentable fraction that also contained bacteria. This study highlights the potential for further study of gepotidacin to fight infections where intracellular niches may play a determining role in bacterial persistence and relapses.
Asunto(s)
Acenaftenos/farmacología , Acenaftenos/farmacocinética , Antibacterianos/farmacología , Antibacterianos/farmacocinética , Compuestos Heterocíclicos con 3 Anillos/farmacología , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Staphylococcus aureus/efectos de los fármacos , Azitromicina/farmacocinética , Azitromicina/farmacología , Línea Celular , Daptomicina/farmacocinética , Daptomicina/farmacología , Humanos , Linezolid/farmacocinética , Linezolid/farmacología , Macrólidos/farmacocinética , Macrólidos/farmacología , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Moxifloxacino/farmacocinética , Moxifloxacino/farmacología , Oxacilina/farmacocinética , Oxacilina/farmacología , Fagocitos/efectos de los fármacos , Células THP-1 , Vancomicina/farmacocinética , Vancomicina/farmacologíaRESUMEN
Gepotidacin (formerly called GSK2140944) is a novel triazaacenaphthylene bacterial topoisomerase inhibitor with in vitro activity against conventional and biothreat pathogens, including Staphylococcus aureus and Streptococcus pneumoniae Using neutropenic murine thigh and lung infection models, the pharmacokinetics-pharmacodynamics (PK-PD) of gepotidacin against S. aureus and S. pneumoniae were characterized. Candidate models were fit to single-dose PK data from uninfected mice (for doses of 16 to 128 mg/kg of body weight given subcutaneously [s.c.]). Dose fractionation studies (1 isolate/organism; 2 to 512 mg/kg/day) and dose-ranging studies (5 isolates/organism; 2 to 2,048 mg/kg/day; MIC ranges of 0.5 to 2 mg/liter for S. aureus and 0.125 to 1 mg/liter for S. pneumoniae) were conducted. The presence of an in vivo postantibiotic effect (PAE) was also evaluated. Relationships between the change from baseline in log10 CFU at 24 h and the ratio of the free-drug plasma area under the concentration-time curve (AUC) to the MIC (AUC/MIC ratio), the ratio of the maximum concentration of drug in plasma (Cmax) to the MIC (Cmax/MIC ratio), and the percentage of a 24-h period that the drug concentration exceeded the MIC (%T>MIC) were evaluated using Hill-type models. Plasma and epithelial lining fluid (ELF) PK data were best fit by a four-compartment model with linear distributional clearances, a capacity-limited clearance, and a first-order absorption rate. The ELF penetration ratio in uninfected mice was 0.65. Since the growth of both organisms was poor in the murine lung infection model, lung efficacy data were not reported. As determined using the murine thigh infection model, the free-drug plasma AUC/MIC ratio was the PK-PD index most closely associated with efficacy (r2 = 0.936 and 0.897 for S. aureus and S. pneumoniae, respectively). Median free-drug plasma AUC/MIC ratios of 13.4 and 58.9 for S. aureus, and 7.86 and 16.9 for S. pneumoniae, were associated with net bacterial stasis and a 1-log10 CFU reduction from baseline, respectively. Dose-independent PAE durations of 3.07 to 12.5 h and 5.25 to 8.46 h were demonstrated for S. aureus and S. pneumoniae, respectively.
Asunto(s)
Acenaftenos/farmacocinética , Antibacterianos/farmacocinética , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Acenaftenos/administración & dosificación , Animales , Antibacterianos/administración & dosificación , Área Bajo la Curva , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Ratones Endogámicos , Pruebas de Sensibilidad Microbiana , Neumonía Estafilocócica/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos , Muslo/microbiologíaRESUMEN
Akt, a serine/threonine protein kinase, is constitutively phosphorylated and hyperactivated in multiple cancers, including acute myeloid leukemia. High levels are linked to poor survival and inferior responses to chemotherapy, making Akt inhibition an attractive therapeutic target. In this phase I/II study of TCN-PM, a small-molecule Akt inhibitor, TCN-PM therapy was well tolerated in patients with advanced hematological malignancies, and reduced levels of phosphorylation of Akt and its substrate Bad were shown, consistent with inhibition of this survival pathway and induction of cell death. Further investigation of TCN-PM alone or in combination in patients with high Akt levels is warranted.
Asunto(s)
Acenaftenos/farmacología , Acenaftenos/farmacocinética , Apoptosis/efectos de los fármacos , Neoplasias Hematológicas/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Ribonucleótidos/farmacología , Ribonucleótidos/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Femenino , Estudios de Seguimiento , Neoplasias Hematológicas/patología , Humanos , Masculino , Persona de Mediana Edad , Fosforilación/efectos de los fármacos , Pronóstico , Distribución Tisular , Células Tumorales Cultivadas , Adulto JovenRESUMEN
PURPOSE: Triciribine phosphate is a potent, small-molecule inhibitor of activation of all three isoforms of AKT in vitro. AKT is an intracellular protein that, when activated, leads to cellular division; it is dysregulated in a large number of malignancies, and constitutively activating AKT mutations are present in a minority of cancers. PATIENTS AND METHODS: In this phase I study triciribine phosphate monohydrate (TCN-PM) was administered to subjects whose tumors displayed evidence of increased AKT phosphorylation (p-AKT) as measured by immunohistochemical analysis (IHC). TCN-PM was administered over 30 min on days 1, 8 and 15 of a 28-day cycle. Tumor biopsy specimens, collected before treatment and on day +15, were assessed for p-AKT by IHC and western blot analyses. RESULTS: Nineteen subjects were enrolled; 13 received at least one cycle of therapy, and a total of 34 complete cycles were delivered. One subject was treated at the 45 mg/m(2) dose before the study was closed due to its primary objective having been met. No dose-limiting toxic effects were observed. Modest decreases in tumor p-AKT following therapy with TCN-PM were observed at the 35 mg/m(2) and 45 mg/m(2) dose levels, although definitive conclusions were limited by the small sample size. CONCLUSIONS: These preliminary data suggest that treatment with TCN-PM inhibits tumor p-AKT at doses that were tolerable. Although single agent activity was not observed in this enriched population, further combination studies of TCN-PM with other signal transduction pathway inhibitors in solid tumors is warranted.
Asunto(s)
Acenaftenos/farmacología , Neoplasias/tratamiento farmacológico , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ribonucleótidos/farmacología , Acenaftenos/efectos adversos , Acenaftenos/farmacocinética , Adulto , Biopsia , Relación Dosis-Respuesta a Droga , Humanos , Mutación , Neoplasias/patología , Ribonucleótidos/efectos adversos , Ribonucleótidos/farmacocinética , Resultado del TratamientoRESUMEN
Roots and above-ground parts (tops) of maize plants, comprising cuticles, leaves and stems, have been exposed separately to polycyclic aromatic hydrocarbons (PAHs) by means of air-tight bicameral exposure devices. Maize roots and tops of plants directly accumulate PAHs from aqueous solutions and from air in proportion to exposure levels. Root and leaf concentration factors (log RCF and log LCF) are log-linear functions of log-based octanol-water partition coefficient (log Kow) and log-based octanol-air partition coefficient (log Koa). The PAHs' concentrations among cuticles, leaves and stems display good correlations with each other. PAH concentrations in each part of the plant tested correlated positively with atmospheric PAHs' concentrations. Comparisons between PAHs' concentrations of root epidermis and root tissue showed similar correlations. Bulk concentrations of contaminants in various plant tissues differed greatly, but these differences disappeared after normalization to lipid contents suggesting lipid-based partitioning of PAHs among maize tissues.