Pharmacokinetics of a Once-Daily Oral Dose of Moxifloxacin (Bay 12-8039), a New Enantiomerically Pure 8-Methoxy Quinolone

ABSTRACT The pharmacokinetics, safety, and tolerability of oral moxifloxacin, a new 8-methoxy quinolone, were assessed in a randomized, double-blind, placebo-controlled study in which healthy male and female volunteers received either 400 mg of moxifloxacin once daily (n = 10) or a placebo once daily (n = 5) for 10 days. Plasma moxifloxacin concentrations on days 1 and 10 were measured by high-performance liquid chromatography and fluorometric detection. Standard pharmacokinetic parameters were estimated by noncompartmental methods. Natural logarithmic estimates for each pharmacokinetic variable of each subject were analyzed by a two-way analysis of variance. Hematology, blood chemistry, vital signs, and adverse events were monitored, and electrocardiograms (ECG) were performed. Plasma moxifloxacin concentrations of predicted therapeutic relevance were achieved in this study. For day 1, the mean maximum concentration of drug in serum (C max) and the area under the concentration-time curve from 0 to 24 h (AUC0–24) were 3.4 mg/liter and 30.2 mg · h/liter, respectively. Corresponding means on day 10 were 4.5 mg/liter and 48 mg · h/liter, respectively. On day 10, the mean elimination half-life was approximately 12 h. Plasma moxifloxacin concentrations exceeded the MIC for Streptococcus pneumoniae throughout the 24-h dosing period. The day 1 and day 10 mean AUC/MIC ratios were 121 and 192, respectively, and the meanC max/MIC ratios were 13 and 18, respectively. Moxifloxacin was well tolerated; no clinically relevant changes in the standard laboratory tests, vital signs, or ECG were observed. Pharmacokinetic parameters demonstrated linearity, and estimates of pharmacokinetic/pharmacodynamic ratios (AUC/MIC andC max/MIC) indicate that the regimen of 400-mg once daily should be effective for treating a variety of infections. Moxifloxacin was found to be safe and well tolerated in healthy volunteers when it was given as a single daily 400-mg dose for 10 days.

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Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00766-12 ◽

2012 ◽

Vol 56 (10) ◽

pp. 5076-5081 ◽

Cited By ~ 39

Author(s):

Keith A. Rodvold ◽

Mark H. Gotfried ◽

J. Gordon Still ◽

Kay Clark ◽

Prabhavathi Fernandes

Keyword(s):

Steady State ◽

High Performance ◽

Healthy Adult ◽

Plasma Concentrations ◽

Epithelial Lining ◽

Time Curve ◽

Epithelial Lining Fluid ◽

Once Daily ◽

Drug Concentrations ◽

The Mean

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.

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Steady-State Pharmacokinetics of Abacavir in Plasma and Intracellular Carbovir Triphosphate following Administration of Abacavir at 600 Milligrams Once Daily and 300 Milligrams Twice Daily in Human Immunodeficiency Virus-Infected Subjects

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01000-08 ◽

2009 ◽

Vol 53 (4) ◽

pp. 1532-1538 ◽

Cited By ~ 32

Author(s):

Graeme Moyle ◽

Marta Boffito ◽

Carl Fletcher ◽

Chris Higgs ◽

Phillip E. Hay ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

High Performance ◽

Pharmacokinetic Parameters ◽

Virologic Suppression ◽

Open Label ◽

Time Curve ◽

Mixed Effect ◽

Once Daily ◽

Immunodeficiency Virus ◽

And Gender

ABSTRACT Abacavir (ABC) is administered either at 600 mg once daily (ABC 600 mg QD) or 300 mg twice daily (ABC 300 mg BID) in anti-human immunodeficiency virus (anti-HIV) combination therapy. Although ABC plasma pharmacokinetics following each regimen has been well defined, no study has directly compared the regimens with respect to pharmacokinetics of ABC's active intracellular anabolite, carbovir-triphosphate (CBV-TP). In an open-label, two-period, crossover study, 34 HIV-infected male and female subjects stabilized on antiretroviral regimens containing either ABC 600 mg QD or ABC 300 mg BID received their usual doses on days −1 and 1 and then switched regimens for days 2 to 11. Serial blood samples collected on days 1 and 11 were assayed for plasma ABC and intracellular CBV-TP concentrations using validated high-performance liquid chromatography-tandem mass spectrometry methods. Pharmacokinetic parameters were calculated using noncompartmental methods. Analysis of variance with a mixed-effect model was performed for treatment and gender comparisons. In 27 evaluable subjects, the regimens provided bioequivalent ABC daily areas under the concentration-time curve from 0 to 24 h (AUC0-24) and comparable CBV-TP concentrations at the end of the dosing interval (C τ). As expected, ABC QD resulted in 109% higher ABC maximum concentrations of drug in plasma (C max) than did ABC BID. ABC QD also resulted in 32% higher CBV-TP AUC0-24 and 99% higher CBV-TP C max than did ABC BID. Females had a 38% higher weight-adjusted ABC AUC0-24 and 81% higher weight-adjusted CBV-TP AUC0-24 than did males. Virologic suppression was maintained during regimen switch, and no tolerability differences between regimens were observed. In conclusion, this study showed that ABC 600 mg QD and ABC 300 mg BID regimens led to similar intracellular CBV-TP C τ values, thus providing pharmacokinetic support for the interchangeability of these two regimens. Women had higher intracellular CBV-TP exposure than did men.

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Pharmacokinetics, Safety, and Tolerability of Ascending Single Doses of Moxifloxacin, a New 8-Methoxy Quinolone, Administered to Healthy Subjects

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.8.2060 ◽

1998 ◽

Vol 42 (8) ◽

pp. 2060-2065 ◽

Cited By ~ 204

Author(s):

H. Stass ◽

A. Dalhoff ◽

D. Kubitza ◽

U. Schühly

Keyword(s):

Clinical Chemistry ◽

Vital Signs ◽

Terminal Phase ◽

Pharmacokinetic Parameters ◽

Active Metabolites ◽

Double Blind ◽

Time Curve ◽

Plasma And Urine Samples ◽

Higher Doses ◽

Binding Level

ABSTRACT The pharmacokinetics of moxifloxacin were investigated in six studies after oral administration of 50, 100, 200, 400, 600, and 800 mg. Eight healthy male volunteers were included in each study. With doses of up to 200 mg the study was performed as a double-blind, randomized group comparison (n = 6 verum andn = 2 matched placebo); with the higher doses the study was conducted with a double-blind, randomized, crossover design. Safety and tolerability were assessed by evaluation of vital signs, electrocardiograms, electroencephalograms, clinical chemistry parameters, results of urinalysis, and adverse events. The drug was well tolerated. The concentrations of moxifloxacin in plasma, urine, and saliva were determined by a validated high-pressure liquid chromatography assay with fluorescence detection. In addition, plasma and urine samples were analyzed by a bioassay. A good correlation between both methods was seen, indicating an absence of major active metabolites. The mean maximum concentrations of moxifloxacin in plasma (C max) ranged from 0.29 mg/liter (50-mg dose) to 4.73 mg/liter (800-mg dose) and were reached 0.5 to 4 h following drug administration. After reaching theC max, plasma moxifloxacin concentrations declined in a biphasic manner. Within 4 to 5 h they fell to about 30 to 55% of the C max, and thereafter a terminal half-life of 11 to 14 h accounted for the major part of the area under the concentration-time curve (AUC). During the absorption phase concentrations in saliva were even higher than those in plasma, whereas in the terminal phase a constant ratio of the concentration in saliva/concentration in plasma of between 0.5 and 1 was observed, indicating a correlation between unbound concentrations in plasma and levels in saliva (protein binding level, approximately 48%). AUC and C max increased proportionally to the dose over the whole range of doses investigated. Urinary excretion amounted to approximately 20% of the dose. Data on renal clearance (40 to 51 ml/min/1.73 m2) indicated partial tubular reabsorption of the drug. The pharmacokinetic parameters derived from compartmental and noncompartmental analyses were in good agreement. The kinetics could be described best by fitting the data to a two-compartment body model.

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Linezolid Pharmacokinetics in Adult Patients with Cystic Fibrosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.1.281-284.2004 ◽

2004 ◽

Vol 48 (1) ◽

pp. 281-284 ◽

Cited By ~ 32

Author(s):

John A. Bosso ◽

Patrick A. Flume ◽

Susan L. Gray

Keyword(s):

Cystic Fibrosis ◽

High Performance ◽

Elimination Rate ◽

Blood Chemistry ◽

Volume Of Distribution ◽

Adult Patients ◽

Pharmacokinetic Parameters ◽

Time Curve ◽

Before And After ◽

Total Body

ABSTRACT The pharmacokinetics of many drugs are altered in patients with cystic fibrosis (CF), often necessitating different dosage requirements than those used in non-CF patients. The objective of this study was to determine the pharmacokinetics of linezolid, an antibiotic with good activity against gram-positive organisms such as methicillin-resistant Staphylococcus aureus, in patients with CF so that dosage requirements could be established. Twelve adult patients (6 male) ranging in age from 22 to 39 years were studied. A single 600-mg dose was administered intravenously over 0.5 h, and plasma samples were collected at 0 (predose), 0.5, 0.75, 1, 2, 4, 8, and 24 h. Linezolid concentrations were determined with a validated high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using standard noncompartmental methods. Blood chemistry and hematologic indices were determined before and after the study for safety purposes. All patients completed the study without encountering any adverse reactions. The pharmacokinetic parameters, while variable, with half-lives varying from 1.76 to 8.36 h, were similar to those previously described in other populations. Mean (± standard deviation) values for pharmacokinetic parameters of interest were as follows: elimination rate constant, 0.21 (0.11) h−1; half-life, 4.41 (2.43); volume of distribution at steady state, 0.87 (0.19) liters/kg of body weight; and total body clearance, 0.12 (0.06) liters/h/kg. No patient would have achieved the pharmacodynamic target of an area under the concentration-time curve/MIC ratio of 83 h for pathogens for which the MIC was 4 μg/ml. Patients with inadequate clinical responses to linezolid may require more frequent dosing.

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Multiple-Dose Pharmacokinetics and Tolerability of Gemifloxacin Administered Orally to Healthy Volunteers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.2.540-545.2001 ◽

2001 ◽

Vol 45 (2) ◽

pp. 540-545 ◽

Cited By ~ 26

Author(s):

Ann Allen ◽

Elizabeth Bygate ◽

Marika Vousden ◽

Stuart Oliver ◽

Martin Johnson ◽

...

Keyword(s):

Maximum Concentration ◽

High Performance ◽

Clinical Chemistry ◽

Clinical Signs ◽

Vital Signs ◽

Terminal Phase ◽

Multiple Dosing ◽

Time Curve ◽

Once Daily ◽

Tract Infections

ABSTRACT Gemifloxacin mesylate (SB-265805-S, LB-20304a) is a potent, novel fluoroquinolone agent with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in two parallel group studies in healthy male volunteers after doses of 160, 320, 480, and 640 mg once daily for 7 days. Multiple serum or plasma and urine samples were collected on days 1 and 7 and were analyzed for gemifloxacin by high-performance liquid chromatography (HPLC)–fluorescence (study 1) or HPLC-mass spectrometry (study 2). Safety assessments included vital signs, 12-lead electrocardiogram (ECG) readings, hematology, clinical chemistry, urinalysis, and adverse experience monitoring. Gemifloxacin was rapidly absorbed, with a time to maximum concentration of approximately 1 h after dosing followed by a biexponential decline in concentration. Generally, maximum concentration and area under the concentration-time curve (AUC) increased linearly with dose after either single or repeat doses. Mean ± standard deviation values of AUC0–τ on day 7 were 4.92 ± 1.08, 9.06 ± 2.20, 12.2 ± 3.69, and 20.1 ± 3.67 μg·h/ml following 160-, 320-, 480-, and 640-mg doses, respectively. The terminal-phase half-life was approximately 7 to 8 h, independent of dose, and was similar following single and repeated administrations. There was minimal accumulation of gemifloxacin after multiple dosing. Approximately 20 to 30% of the administered dose was excreted unchanged in the urine. The renal clearance was 160 ml/min on average after single and multiple doses, which was slightly greater than the accepted glomerular filtration rate (approximately 120 ml/min). These data show that the pharmacokinetics of gemifloxacin are linear and independent of dose. Gemifloxacin was generally well tolerated, although one subject was withdrawn from the study after 6 days at 640 mg for mild, transient elevations of alanine aminotransferase and aspartate aminotransferase not associated with any clinical signs or symptoms. There were no other significant changes in clinical chemistry, hematology or urinalysis parameters, vital signs, or ECG readings. In conclusion, the results of these studies, combined with the antibacterial spectrum and potency, support the further investigation of once-daily administration of gemifloxacin for indications such as respiratory tract and urinary tract infections.

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A pilot study on the pharmacokinetics of a single intramuscular injection of cefquinome in Arabian camel calves

Acta Veterinaria Hungarica ◽

10.1556/004.2020.00008 ◽

2020 ◽

Vol 68 (1) ◽

pp. 59-64

Author(s):

Abdullah Altayban ◽

Mahmoud Kandeel ◽

Yukio Kitade ◽

Mohammed Al-nazawi

Keyword(s):

Intramuscular Injection ◽

High Performance ◽

Pharmacokinetic Parameters ◽

Beta Lactams ◽

Time Curve ◽

Elimination Phase ◽

Single Intramuscular Injection ◽

Elimination Half ◽

The Mean ◽

Arabian Camel

AbstractThis study was conducted to evaluate the pharmacokinetics of cefquinome in camel calves after a single intramuscular injection in a dose of 2 mg/kg body weight (kg b. w.). Cefquinome concentrations were measured by ultra-high performance liquid chromatography–mass spectrometry (UPLC-MS/MS). A non-compartmental pharmacokinetic model was used to fit the time–concentration curve and estimate the pharmacokinetic parameters. The peak serum concentration (Cmax) was 28.4 μg/mL at the time of maximum concentration (Tmax) of 25 min. The elimination half-life (t1/2) was 17.4 h. The area under the concentration–time curve (AUC0–∞) was 103.7 μg/ml−1h and the mean residence time (MRT0–∞) was 21.3 h. In comparison with other animal species, the pharmacokinetics of cefquinome in Arabian camel calves showed faster absorption from the site of injection and slower elimination. Since cefquinome, as other beta-lactams, is a time-dependent antimicrobial agent, a single dose of 2 mg/kg b. w. might be sufficient against the most sensitive organisms in camel calves owing to its prolonged elimination phase. However, dose readjustment is required for cases needing concentrations above 2 µg/mL for 12 h or above 1 µg/mL for 24 h.

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Pharmacokinetics and Tolerability of Gemifloxacin (SB-265805) after Administration of Single Oral Doses to Healthy Volunteers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.6.1604-1608.2000 ◽

2000 ◽

Vol 44 (6) ◽

pp. 1604-1608 ◽

Cited By ~ 50

Author(s):

Ann Allen ◽

Elizabeth Bygate ◽

Stuart Oliver ◽

Martin Johnson ◽

Christopher Ward ◽

...

Keyword(s):

High Performance ◽

Clinical Chemistry ◽

Vital Signs ◽

Pharmacokinetic Profile ◽

Terminal Phase ◽

Time Curve ◽

Once Daily ◽

Elimination Half ◽

Safety Assessments ◽

Oral Doses

ABSTRACT Gemifloxacin (known as SB-265805 or LB-20304) is a potent, novel fluoroquinolone compound with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in healthy male volunteers after a single dose of 20, 40, 80, 160, 320, 600, or 800 mg. Multiple serum and urine samples were collected and analyzed for gemifloxacin using high-performance liquid chromatography with fluorescence detection. Safety assessments included vital signs, 12-lead electrocardiogram readings, hematology, clinical chemistry, urinalysis, and adverse-experience monitoring. Gemifloxacin was rapidly absorbed after all doses. Maximum concentrations of gemifloxacin in serum (C max) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values ofC max and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC0–∞) increased linearly with dose. Serum AUC0–∞ values (mean ± standard deviation) were 0.65 ± 0.01, 1.28 ± 0.22, 2.54 ± 0.31, 5.48 ± 1.24, 9.82 ± 2.70, 24.4 ± 7.1, and 31.4 ± 7.6 μg · h/ml following 20-, 40-, 80-, 160-, 320-, 600-, and 800-mg doses, respectively. The terminal phase elimination half-life was independent of dose, with an overall mean of 7.4 ± 2.0 h. The profiles indicated that the pharmacokinetic profile is suitable for a once-daily dosing regimen. Approximately 25 to 40% of the administered dose was excreted unchanged in the urine, and renal clearance (ca. 150 ml/min) was independent of dose. There were no significant changes in clinical chemistry, hematology, or urinalysis parameters, vital signs, or 12-lead electrocardiogram readings in subjects, irrespective of dose. The results of these studies support the further investigation of once-daily administration of gemifloxacin.

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SAFETY OF AMISELIMOD IN HEALTHY SUBJECTS: RESULTS FROM A PHASE 1 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.001 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S1-S1

Author(s):

Stephen Hanauer ◽

Terry O’Reilly ◽

Robert Lester ◽

Neal Slatkin ◽

Jimin Lee ◽

...

Keyword(s):

Single Dose ◽

Healthy Subjects ◽

Vital Signs ◽

Controlled Study ◽

Tolerability Profile ◽

Double Blind ◽

Study Drug Administration ◽

Safety Population ◽

Physical Examinations ◽

The Mean

Abstract Objective To evaluate the safety profile of amiselimod, a selective sphingosine 1-phosphate receptor modulator which has been shown to regulate lymphocyte trafficking and is in development for the treatment of inflammatory bowel disease. Methods A randomized, double-blind, multiple-dose, placebo-controlled, parallel study with a nested crossover design evaluated the safety and tolerability profile of amiselimod. Healthy adults were randomized in a 2:1:1 ratio during a 28-day treatment period accordingly: a single dose of placebo followed by oral amiselimod (upwardly titrated in doses ranging from 0.4 to 1.6 mg to achieve 0.4 mg and 0.8 mg steady-state exposure; a single dose of oral moxifloxacin 400 mg followed by placebo; or placebo followed by a single dose of moxifloxacin 400 mg. The safety population included all subjects who received at least one dose of treatment. Adverse events (AE) and serious AEs were collected. Treatment-emergent AEs were defined as an AE that was starting or worsening at the time of or after study drug administration. Changes in clinical laboratory parameters (including lymphocyte counts), physical examinations, vital signs, and electrocardiogram parameters (including heart rate, PR, QRS, and QT intervals) were recorded. Subjects were permitted to withdraw if lymphocyte counts were ≤ 0.2 x 109/L. Results The safety population included 190 subjects of which 95 received amiselimod and 95 were in the combined moxifloxacin group. Subjects were 40% female, 83% white, and the mean (standard deviation) age was 39.0 (8.8) years. The discontinuation rate was 8% (n=8) in the amiselimod group and 4% (n=4) in the moxifloxacin group. Three subjects who received amiselimod discontinued because they met the stopping criteria for low lymphocyte counts. One subject experienced an amiselimod-related serious AE of atrial fibrillation on day 26 (after receiving amiselimod 1.6 mg for 3 of the preceding 4 days) that required hospitalization, cardioversion, and led to discontinuation. No deaths were reported. All other AEs were mild to moderate in severity. Decreased white blood counts were the most commonly reported TEAE, followed by headache and constipation (Table). Reductions in white blood counts returned to normal range after study discontinuation without sequelae. Decreased neutrophils, lymphocytes and hemoglobin, and increased creatine kinase, alanine aminotransferase, and aspartate aminotransferase were reported, all of which resolved without sequelae. The mean absolute lymphocyte count for amiselimod exhibited a gradual decrease from predose (1.681 thou/uL) to a nadir of 0.424 thou/uL on day 27 (Figure). Changes to vital signs, physical examinations, and ECG parameters were within normal limits. Conclusions Upwardly titrated doses of amiselimod ranging from 0.4 to 1.6 mg were generally well tolerated in healthy subjects.

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Results of a Double-Blind, Randomized, Placebo-Controlled Phase 1 Study to Evaluate the Safety and Pharmacokinetics of Anti-Zika Virus Immunoglobulin

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.20-1578 ◽

2021 ◽

Author(s):

Jane White ◽

Priya Tunga ◽

Deborah M. Anderson ◽

Ken Iledan ◽

Tobi Loreth ◽

...

Keyword(s):

Coefficient Of Variation ◽

Zika Virus ◽

Healthy Adult ◽

Phase 1 ◽

Vital Signs ◽

Controlled Study ◽

Pharmacokinetic Analysis ◽

Double Blind ◽

Time Curve ◽

Laboratory Test Results

Zika virus (ZIKV) is transmitted primarily through infected Aedes aegypti or Aedes albopictus mosquitoes. ZIKV infection during pregnancy was linked to adverse fetal/infant outcomes, including microcephaly, brain anomalies, ocular disorders, intrauterine growth restriction, and other congenital malformations. Human anti-Zika virus immunoglobulin (ZIKV-Ig) is being developed for prophylaxis of ZIKV in at-risk populations, including women of childbearing potential and pregnant women. A phase 1 single-center, double-blind, randomized, placebo-controlled study was conducted to assess the safety and pharmacokinetics (PK) of a single 50.0-mL ZIKV-Ig intravenous dose in healthy adult male or non-pregnant female subjects 18 to 55 years of age. Subjects received either ZIKV-Ig (n = 19) or saline placebo (n = 11). Safety was evaluated based on adverse events (AEs), laboratory test results, physical examinations, and vital signs. Overall, there were 11 subjects (36.7%) with treatment-related AEs including eight subjects (42.1%) in the ZIKV-Ig group and three subjects (27.3%) in the placebo group. Of the AEs considered treatment related, three subjects (15.8%) experienced headache (mild). There were no serious AEs, no deaths, and no discontinuations resulting from AEs. Overall, the safety profile of ZIKV-Ig in this study population of healthy adult subjects appeared to be safe and well tolerated. The results of the pharmacokinetic analysis determined that ZIKV-Ig had a maximum observed concentration of 182.3 U/mL (coefficient of variation, 21.3%), the time at which Cmax occurred of 2.3 hours ± 1.0 (SD), an area under the concentration–time curve0–∞ of 77,224 h × U/mL (coefficient of variation, 17.9%), and a half-life of 28.1 days, which is similar to other human-derived commercial Ig intravenous products.

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