Variability of Sulfotransferase 1A1 Activity in Humans: an Approach to Improve Predictive Drug Response - Part I: Analysis of Intraindividual Variation in Healthy Adults

Hospital da Luz, Portugal

Status and phase

Completed

Phase 1

Conditions

Healthy Volunteers

Treatments

Drug: Paracetamol

Study type

Interventional

Funder types

Other

Identifiers

NCT03182595

HLUZ_001_2016

Details and patient eligibility

About

An open-label, single centre, nonrandomized clinical study in healthy volunteers, with intervention over a 13---week period. After written informed consent, subjects will undergo screening evaluations (Visit 1). One week after visit 1, subjects who meet the selection criteria will enter a run---in period of 8 weeks where participants will receive paracetamol 1g tablet and collect a blood sample at monthly intervals (visits 2, 3 and 4). A final visit for safety assessment will take place at week 13 (visit 5). Blood samples will be used to quantify P, PG e PS.

Full description

To be able to predict efficacy and adverse reactions involving compounds metabolized by sulfonation, the investigators need more information on SULTs. Studies of in vivo sulfonation in humans are lacking, although they are of key importance in assessing the functional consequences of individual variation. In our current study, the investigators will start by developing an HPLC method of quantifying SULT1A1 activity using paracetamol as probe substrate and studying intraindividual variation in healthy adults. Advantages of using paracetamol as a probe substrate for in vivo phenotyping of SULT1A1 include: wide safety margin for in vivo use, easy and ready administration of the drug, significant metabolism by the enzyme of interest, short half---life, linear pharmacokinetics over a wide concentration range and a limited number of metabolites, quantifiable in plasma.15,24 In a subsequent study, the investigators plan to study interindividual variation in a larger sample, including subjects with chronic disease and on medication.The investigators expect to provide a valuable new tool to explore the clinical significance of variation of SULT1A1 activity, the most important SULT on drug metabolism.

Enrollment

36 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy males and females, over 18 years of age,
Informed of the nature of the study and giving written informed consent,
Report no significant diseases during screening,
Have normal CBC, renal function and liver enzymology,
Have no contraindication for paracetamol,
Be on no regular medical treatment, except for contraceptives,
Be able to communicate effectively with study personnel.

Exclusion criteria

Hypersensitivity or idiosyncratic reaction to paracetamol,
Intake of any medication, except for contraceptives, within 14 days before start of the study,
Pregnancy or breastfeeding,
BMI <18 kg/m2,
Participation in a clinical study of any investigational product 1 month prior to visit 1 or during the study.