The goal of this observational study aims to reveal the pharmacokinetics of clinical probes and characteristics of endogenous biomarkers for drug-metabolizing enzymes and transporters in Chinese older adults and old older adults, to analyze their correlation with frailty, and to explore the exosome characteristics in this population.

This study is a non-intervention observational study in Chinese older adults and will not interfere with the routine medical treatment. 6-10 mL whole blood and 20 mL urine samples (only applicable for patients taking meropenem and metformin) will be collected from eligible subjects according to medical routine blood collection time. Concentration of clinical probes and respective metabolites (when required), endogenous biomarkers, genotype information of drug-metabolizing enzymes and transporters, and the exosome characteristics will be quantified or measured.

Inclusion Criteria:

1. Older adults males and females aged 60-74 years old (older adults group) and ≥75 years old (old older adults group), proportion of either sex must not be less than 1/3 (except for subjects taking finasteride), number of subjects in each frailty category must not be less than 10;
2. Male participants must weight ≥45 kg and female participants must weight ≥40 kg. Body mass index (BMI) must be within the range of 18.0-28.0 (inclusive). BMI = weight (kg)/height^2 (m^2);
3. Inpatients with stable underlying disease, who takes any one or more of the following clinical probes: omeprazole/rabeprazole/pantoprazole/metoprolol/carvedilol/rivaroxaban/amlodipine/finasteride/simvastatin/meropenem/atorvastatin/rosuvastatin/metformin;
4. Creatinine clearance (CRCL) ≥15 mL/min, calculated by CockCroft-Gault equation. CRCL = [(140-age)*(lean body weight, kg)*(0.85 if female)/(72*Scr, mg/dL);
5. Willingness to comply with the study protocol and sign informed consent form.

Exclusion Criteria:

1. Subjects with known history of blood phobia or needle phobia that would preclude safe participation in the study procedures.

2. History of disease or an emerging disease within the past 1 month that could affect the study: Diseases affecting the abundance and activity of liver drug enzymes or transporters: cancer, diabetes (except metformin group), acute kidney injury, liver disease (cirrhosis, liver cancer, severe liver injury, severe fatty liver, liver abscess, internal bile duct stones, etc.)

3. History of major diseases or newly discovered diseases: prostate cancer, leukemia, liver cancer, breast cancer, colorectal cancer, leukemia and other tumor diseases;

4. Drugs that may affect the study were consumed within 1 week prior to screening:

   • Patients taking omeprazole/rabeprazole/pantoprazole: Potent CYP2C19 inhibitors: ASP8477, fluconazole, fluoxetine, fluvoxamine, ticlopidine; Potent CYP2C19 inducers: apalutamide, rifampicin, ritonavir;
   • Patients taking metoprolol/carvedilol: Potent CYP2D6 inhibitors: ASP8477, bupropion, fluoxetine, paroxetine, quinidine
   • Patients taking rivaroxaban/amlodipine/finasteride/simvastatin/atorvastatin: Potent CYP3A inhibitor: boceprevir, ceritinib, conivaptan hydrochloride, verapamil, diltiazem, aprepitant, quinidine, dronedarone, tacrolimus, protease inhibitors (ritonavir, indinavir, nelfinavir, saquinavir, lopinavir), macrolides antibiotics (erythromycin, clarithromycin, telithromycin), chloramphenicol, antifungal drugs (ketoconazole, itraconazole, posaconazole, voriconazole, fluconazole, miconazole) nefazoldone, cobistat, cimetidine, ciprofloxacin, fluvoxamine, imatinib, St. John's wort, ranolazine; Potent CYP3A inducers: apalutamide, avomibe, rifampicin, carbamazepine, enzalutamide, ivosidenib, mitotane, phenytoin, rifapentine
   • Patients taking meropenem: Potent OAT inhibitors: aminohippuric acid, probenecid, teriflunomide
   • Patients taking simvastatin/atorvastatin/rosuvastatin: Potent OATP1B1 inhibitor: protease inhibitor (atazanavir, ritonavir, lopinavir, simeprevir), cyclosporin, macrolides antibiotics (erythromycin, clarithromycin), rifampicin;

5. Subjects who have smoking addict or alcohol abuse and do not agree to abstain from smoking or drinking during the trial period (smoking addict: average of ≥5 cigarettes daily; alcohol abuse: average of ≥100mL hard liquor);

6. Tested positive on virological test (human immunodeficiency virus antibody (HIV-Ab)), syphilis serological test, hepatitis B virus surface antigen (HBsAg), or hepatitis C virus antibody (HCV-Ab) within 6 months prior to screening;

7. Subjects who have participated in clinical trials of any drug or medical device within 3 months prior to screening;

8. Subjects who have any factors deemed unsuitable for participation in this study.](streamdown:incomplete-link)

Inpatients aged 60-74 years old (older adults group) and ≥75 years old (old older adults group) with stable underlying disease, takes any one or more of the following clinical probes: omeprazole/rabeprazole/pantoprazole/metoprolol/carvedilol/rivaroxaban/amlodipine/finasteride/simvastatin/meropenem/atorvastatin/rosuvastatin/metformin.