To Evaluate Plasma and Pulmonary Pharmacokinetics of GSK2140944

Antimicrobial penetration can be assessed through evaluation of antimicrobial concentrations in various lung compartments, including bronchial mucosal tissue, epithelial lining fluid (ELF), and alveolar macrophages (AM). Antimicrobial concentrations determined in ELF and alveolar macrophages represent an ideal estimate of concentrations at the site of infection and can be accessed via bronchoalveolar lavage (BAL). However sampling of antimicrobial concentrations via BAL is not routine in clinical practice due to its complex methodology and poor patient tolerability. This study will evaluate intrapulmonary and plasma pharmacokinetics of GSK2140944 after single IV dose in adult healthy volunteers. This is a Phase I, open-label study to evaluate plasma and pulmonary pharmacokinetics following intravenous administration of GSK2140944 in healthy adult participants. Part A will evaluate the single dose PK profiles. Part B is optional and will only be conducted if necessary. Each part will consist of a maximum of 6 cohorts. In Part A, only 4 of the 6 cohorts will be dosed initially; cohorts 5 and 6 are optional and will only be dosed if additional time-points are necessary to adequately model the pulmonary pharmacokinetic profile.


Eligibility Criteria:
Inclusion Criteria:

* Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin \<=1.5x Upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, vital signs, electrocardiograms (ECGs), physical examination, and laboratory tests. A participant with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included if in the Investigator's judgement the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
* Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent. A female participant is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. To confirm post-menopausal status, a blood sample for simultaneous follicle stimulating hormone (FSH) \> 40 milli-international units per milliliter (MlU/ml) and estradiol \< 40 picrograms (pg)/ml (\<147 picromoles/Liter \[pmol/L\]) is confirmatory. Male participant with female partners of child-bearing potential must agree to use one of the contraception methods listed as per protocol. This criterion must be followed from the time of the first dose of study medication until the final follow-up visit.
* Body weight \>= 50 kg and Body mass index (BMI) within the range 19 - 31Kilograms/meter\^2(kg/m\^2) (inclusive).
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

* Contraindications to bronchoalveolar lavage including hypercapnia \>50 millimeters of mercury (mm Hg), known or suspected intolerability to medications necessary for bronchoscopy, refractory hypoxemia, reactive airway disease or asthma, unstable angina or acute myocardial infarction in the last 6 months, heart failure, and severe hemostatic alterations.
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or positive Human Immunodeficiency Virus (HIV) antibody.
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Any clinically significant central nervous system (e.g., seizures), cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions or history of such conditions that, in the opinion of the investigator may place the participant at an unacceptable risk as a participant in this trial or may interfere with the absorption, distribution, metabolism or excretion of drugs.
* A positive urine test for drugs of abuse or alcohol (or alcohol breath test) at screening.
* A screening urinalysis positive for protein or glucose (greater than "trace" findings of protein or glucose).
* A serum creatinine value that is out of the normal range, or an increase of 0.2 milligrams/decilitre (mg/dL) (or 15.25 micromoles/Liters \[µmol/L\]) in serum creatinine value between screening and Day -1 visit.
* History of photosensitivity to quinolones.
* Unwillingness to commit to avoid excessive exposure to sunlight (or exposure whilst on a tanning bed) which would cause a sunburn reaction from first dose up to and including the follow-up visit.
* History of drug abuse within 6 months of the study or a history of smoking or use of nicotine containing products within 3 months of screening, or a positive urine cotinine indicative of smoking at screening.
* History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
* The participant has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
* Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, or use of St. John's Wort within 14 days prior to the first dose of study medication. By exception, the volunteer may take paracetamol or acetaminophen (\<=2 grams/day) up to 48 hours prior to the first dose of study medication. However, the Investigator and GSK study team can review medication on a case by case basis to determine if its use would compromise participant safety or interfere with the study procedures or data interpretation.
* History of sensitivity to any of the study medications, including GSK2140944 and those that may be used in association with the BAL procedure, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
* Donation of blood in excess of 500 mL within 12 weeks prior to dosing.
* History of tendon rupture.
* History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinical research unit uses heparin to maintain intravenous cannula patency).
* Consumption of red wine, pomegranate, seville oranges, grapefruit or grapefruit juice, pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices containing such products from 7 days prior to the first dose of study medication.
* Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart Rate, Males \<40 and \>100 Beat Per Minute (bpm), females \<50 and \>100 bpm; PR interval \<120 and \>220 msec; QRS duration \<70 and \>100 msec; A QT interval corrected for heart rate using the Bazett's formula (QTcB) or Single QT duration corrected for heart rate by Fridericia's formula (QTcF) interval \>450 msec. Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization). A participant has Bundle Branch Block. Any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block \[2nd degree or higher\], Wolf Parkinson White \[WPW\] syndrome), sinus pauses\>3 seconds, non-sustained or sustained ventricular tachycardia (\>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual participant.