(Morbid) obesity overweight
Conditions
Interventions
In this study, the intervention consists of the administration of one dose of
the investigational drug (gentamicin, tobramycin, vancomycin or ciprofloxacin).
- 5 mg/kg LBW (for obese participants,
for healthy volunteers 500 mg PO followed after 3 hours by
ciprofloxacin 400 mg IV (n=8). For obese participants 500mg PO or
ciprofloxacin 400mg IV (n = 20)
LBW is calculated using the Janmahasati
Sponsors
Sint Antonius Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria for (morbidly) obese participants: - Indication for bariatric surgery (i.e. BMI > 40 kg/m2 or BMI > 35 kg/m2 with additional risk factors). Bariatric surgery includes the following: laparoscopic gastric bypass surgery or laparoscopic sleeve gastrectomy. We will equally stratify subjects to 4 weight groups: 100-120 kg, 120-145 kg, 145-170 kg and >170 kg; - Participants between 18 - 60 years old; - ASA physical classification of II or III; - Participant is able and willing to sign the Informed Consent before screening evaluations.;Inclusion criteria for controls (normal weight participants): - BMI between 18 and 25 kg/m2; - Participants between 18 - 55 years old;
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study:;- Known allergy to the administered drug; - Recent use of the study drug (up to 7 days before administration of the study drug); - Treatment with the concerning study drug up to 7 days before administration of the study drug. - Pregnancy or breastfeeding. This is an exclusion criteria for bariatric surgery as well (participants are informed by their surgeon and bariatric nurse). Women of childbearing potential using contraception are allowed to participate in the study.;Specific exclusion criteria for participants receiving an aminoglycoside or vancomycin: - Renal insufficiency identified by eGFR 3 times upper limit of normal values) - Known prolonged QT-interval or participants that use drugs that are known to prolong the QT-interval (based on the list published by CredibleMeds®, formerly known as AZCERT) - Epilepsy - Myasthenia gravis - Porphyria cutanea tarda - Psychoses in history - Participants that use drugs that are known to be metabolized by CYP1A2 or CYP3A4;Additional exclusion criteria for participants receiving ciprofloxacin PO:;- Participants that use oral drugs that contain bivalent cations (calcium, magnesium, aluminum or iron), phosphate binders (sevelamer) or sucralphate, influence gastric emptying or antacids less than 6 hours before administration of ciprofloxacin.;For healthy volunteers a few extra prohibitions apply to participation (these are standard prohibitions employed in the CRCN): - Water is allowed as desired except for one hour before and one hour after administration of study medication. - From four hours after dosing until release of confinement, consumption of available beverages is free and meals are standardized in regard to consumption and time of administration. - No history of alcohol or drugs abuse (up until one month before study drug administration). - Subjects may not consume alcoholic beverages from 24 hours before until 48 hours after administration of study medication. - Subjects may not use grapefruit containing food or juice, or St John*s worth, from 7 days before until the end of the study. - Female subjects of childbearing potential without adequate contraception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double ba
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint is clearance (Cl) of gentamicin, tobramycin, vancomycin or ciprofloxacin in obese participants versus normal weight participants. Other primary endpoints are volume of distribution (Vd) for all four drugs and oral bioavailability (F) for ciprofloxacin in obese participants versus normal weight participants. | — |
Secondary
| Measure | Time frame |
|---|---|
| Influence of covariates (total bodyweight, lean bodyweight, gender, length, age, creatinine, metabolomic profile, history/duration of obesity (estimation of number of years the patient fulfils definition of morbid obesity), GFR) on primary parameters of interest (i.e. clearance and volume of distribution). The covariate *metabolomic profile* means that we want to investigate the influence of the metabolism of several endogen components on the different PK-parameters. Other study parameters: GFR measured using creatinine concentration in urine collected over 24 hours in morbidly obese participants. | — |
Countries
Netherlands
Outcome results
None listed