Handbook of Creatine and Creatinine In Vivo Kinetics Production, Distribution, Metabolism, and Excretion

Chapter 1.  Production of Creatine (CR) and Creatinine (Cr)

1.1 Preliminaries: Chemical and Biological Properties of Creatine and Creatinine

1.1.1 Chemical Characteristics of Creatine

1.1.2 Biosynthesis and Distribution of Creatine

1.1.3 Chemical Characteristics and Formation of Creatinine

1.1.4 Solubility and Distribution of Creatine and Creatinine

1.1.5 Clinical Relevance and Excretion of Creatinine

1.1.6 Crystal Structures

1.2 In Vivo Biosynthesis of Creatine

1.2.1 Precursors of Creatine

1.2.2 Pathway of Creatine Biosynthesis

1.2.3 Methylation of Guanidinoacetic Acid

1.2.4 Precursors and Biosynthesis of Creatinine

1.2.4.1 Influence of pH on Creatine–Creatinine Interconversion

1.2.4.2 Conversion in Alkaline Media

1.2.5 Kinetics of Creatine Transformation

1.2.6 Formation of Creatinine from Phosphocreatine

1.2.7 Chemokinetic Modeling of Creatinine Formation

1.2.7.1 Phosphocreatinine as an Intermediate in Creatinine Formation

1.2.8 Enzymes Involved in Creatine Biosynthesis

1.2.8.1 L-Arginine:Glycine Amidinotransferase (AGAT; EC 2.1.4.1)

1.2.8.1.1 AGAT-Mediated Transfer to Lysine and Homoarginine Formation

1.2.8.1.2 Summary of AGAT-Catalyzed Reactions

1.2.8.1.3 Equilibrium of AGAT-Catalyzed Reactions and Clinical Implications

1.2.8.1.4 Consequences of AGAT Deficiency

1.2.8.1.5 Regulation of AGAT Expression by Creatine Levels

1.2.8.2 Guanidinoacetate N-methyl Transferase (GAMT, EC 2.1.1.2)

1.2.8.2.1 GAMT Distribution and Function

1.2.8.2.2 Kinetic Regulation of GAMT Activity

1.2.8.2.3 Regulation and Physiological Relevance

1.2.9 Creatine Kinase (CK) (EC 2.7.3.2)

1.2.9.1 Cellular Localization and Structure

1.2.9.2 Mitochondrial Creatine Kinase

1.2.9.3 Clinical Relevance and Biomarker Utility

1.2.9.4 Factors Influencing CK Levels

1.3 Creatine Transporter – SLC6A8

1.4 ATP and Creatine Phosphorylation

1.4.1 ATP Production and Utilization

1.4.2 Enzymatic Regulation and Cellular Homeostasis

1.4.3 Role of Phosphagens and Creatine Kinase

1.4.4 Skeletal Muscle Creatine and Phosphocreatine

1.4.5 Cellular Energy Regulation and AMPK Activation

1.4.6 Creatine’s Role in Muscle Oxygen Consumption and Contraction

1.4.7 Cardiac Creatine and Phosphocreatine

1.4.8 Central Nervous System Creatine and Phosphocreatine

1.4.9 Testicular Creatine and Phosphocreatine

1.4.10 Pancreatic Creatine and Phosphocreatine

References

Chapter 2. In Vivo Distribution of Endogenous Creatine (CR) and Creatinine (Cr) 2.1 Contrast of Creatine and Creatinine Physiological Profile

2.1.1 Presumption of Steady State

2.2 Systemic Distribution of Creatine (CR) and Creatinine (Cr)

2.2.1 Creatine In Vivo Distribution

2.2.2 Creatinine In Vivo Distribution

2.2.3 Factors Influencing the In Vivo Distribution of Creatine (CR) and Creatinine (Cr)

2.2.3.1 Influence of Total Body Water (TBW)

2.2.3.2 Interaction with Human Serum Albumin

2.2.3.3 Role of Red Blood Cells

2.2.3.4 Creatine (CR) and Creatinine (Cr) Interactions with Physiological Barriers

2.2.3.4.1 Blood-Brain Barrier

2.2.3.4.2 Blood-CSF Barrier

2.2.3.4.3 Placenta Barrier

2.2.3.4.4 Blood-Testis Barrier (BTB)

2.2.3.4.5 Blood–Aqueous Humor Barrier (BAB)

2.2.3.4.6 Blood Retinal Barrier (BRB)

2.2.3.5 Skeletal Muscle Mass Measurement

2.2.3.5.1 Empirical Equations Based on Weight and Height

2.2.3.5.2 Whole-Body Dual-Energy X-ray Absorptiometry (DXA)

2.2.3.5.3 Skeletal Muscle Mass Estimation Using Creatine (CR) – Isotopic Dilution Method

2.2.3.5.4 Skeletal Muscle Mass Estimation Using Creatinine (Cr)

2.2.3.6 Effect of Blood Flow on Distribution of Endogenous Creatine (CR) and Creatinine (Cr) - Influence of Preferential Uptake of Creatine by Muscle

2.2.3.6.1 Perfusion-Limited Distribution of Creatine (CR)

2.2.3.6.2 Permeability-Limited Distribution of Creatinine (Cr)

References

Chapter 3.       Elimination (Metabolism and Excretion) of Creatine (CR) and Creatinine (Cr) 3.1 Excretion and Metabolism of Creatine (CR)

3.1.1 Urinary Excretion of Creatine (CR)

3.1.2 Non-urinary Reduction of Creatine (CR) Plasma Concentration

3.1.3 Influence of Intestinal Microbiotas on Exogenous Creatine (CR)

3.1.4 In Vivo Creatine (CR) Metabolism

3.2 Excretion and Metabolism of Creatinine (Cr)

3.2.1 Background

3.2.2 Creatinine Coefficient

3.2.3 Exogenous versus Endogenous Creatinine (Cr) Clearance

3.2.4 Circadian Rhythm and Diurnal Excretion of Creatinine

3.2.5 In Vivo Creatinine (Cr) Metabolism

3.2.5.1 Excretion Rate of Creatinine in Relation to Its Hydration Rate In Vivo

3.2.5.2 Labeled Creatinine: Indications and Comparative Analysis of [amidino-14C]-Cr versus [carbonyl-14C]-Cr

3.2.6 Metabolism of Creatinine (Cr) by Gut Microbiota

3.2.7 Influence of Diet, Activity, and Body Composition on Creatinine Production / Excretion

References

Chapter 4. Mathematical Models of Creatine (CR) and Creatinine (Cr)

4.1             Background

Part One: Creatinine Models

4.2  Creatinine (Cr) Linear Models

4.2.1          Compartmental Analysis and Distribution Volume(s) of Creatinine (Cr)

4.2.1.1    Experimental Volumes of Distribution and Kinetics of Creatinine in Dogs

4.2.2 Distribution of Creatinine in Body Water

4.2.3 Two-Compartment Analysis and Clearance Calculations

4.2.3.1 Volume of Distribution and Comparison with Previous Studies

4.2.3.2 Estimation of Renal Dead Space

4.2.3.3 Model Parameters and Constants

4.2.3.4 Comparison with Conventional Two-Compartment Analysis

4.2.3.5 Clearance Definitions in Two-Compartment Models

4.2.4 Creatinine (Cr) In Vivo Kinetics in Humans – Two-Compartment Model

4.2.5 Creatinine (Cr) In Vivo Kinetics in Rabbits – Two-Compartment Model

4.2.6 Creatinine (Cr) In Vivo Kinetics in Humans – One-Compartment Model

4.3 Mechanistic and Physiological Models of Creatinine Kinetics

4.3.1 Quasi Steady State Model for Creatinine (Cr) in Neonates

4.3.2 Physiological/Mechanistic Based Model of Creatinine Renal Disposition

4.3.2.1 Physiological Structure and Compartmental Dynamics

4.3.2.2 Steady-State Creatinine Clearance

4.4 Creatinine (Cr) Kinetic Modeling for Unsteady-State Serum Levels in Acute Renal Failure

4.4.1 Model Assumptions

4.4.1.1 Mathematical Formulation

4.4.2 Application and Limitations

Part Two: Creatine Models

4.5 Introduction

Differences between CR and Cr kinetics

4.5.1 Linear One-Compartment Model

4.5.2 Nonlinear Tissue Binding Model: Heterogeneous One-Compartment Open Model

4.5.3 Mitochondrial–Cytoplasmic Cellular Two-Compartment Model of Creatine (CR) and Creatine Phosphate (PCR)

References

Chapter 5.   Creatine (CR) and Creatinine (Cr) as Biological Markers

5.1 Background

5.2 Creatine (CR) as Biomarker

5.2.1 Creatine Deficiency Syndromes (CDS)

5.2.1.1 AGAT Deficiency

5.2.1.2 GAMT Deficiency

5.2.1.3 SLC6A8 (CRTR) Deficiency

5.3 Creatinine (Cr) as Biomarker

5.3.1 Relationship Between Endogenous Creatinine Clearance and Serum Creatinine - Background

5.3.2 Empirical Formulas for Estimating GFR from Serum Creatinine

5.3.2.1 Empirical Equations to Estimate Creatinine Clearance or Glomerular Filtration Rate Using Serum Creatinine (1957–2025)

5.3.2.1.1 Effersøe Equations (1957)

5.3.2.1.2 Edward and Whyte Equations (1959)

5.3.2.1.3 Doolan et al. Equations (1962)

5.3.2.1.4 Enger and Blegen Equation (1964)

5.3.2.1.5 Jelliffe Equation (1971)

5.3.2.1.6 Siersbæk-Nielsen et al. Nomogram (1971)

5.3.2.1.7 Jelliffe and Jelliffe Equations (1972)

5.3.2.1.8 Mawer Equations (1972)

5.3.2.1.9 Jelliffe Equations (1973)

5.3.2.1.10 Kampmann et al. Equation (1974)

5.3.2.1.11 Cockcroft and Gault Equation (1976)

5.3.2.1.12 Rowe et al. Equation (1976)

5.3.2.1.13 Schwartz et al. Equation (1976)

5.3.2.1.14 Counahan et al. Equation (1976)

5.3.2.1.15 Shull et al. Equation (1978)

5.3.2.1.16 Bjornsson Equations (1979)

5.3.2.1.17 Hull et al. Equations (1981)

5.3.2.1.18 Bjornsson et al. (1983)

5.3.2.1.19 Gates Equation (1985)

5.3.2.1.20 Salazar and Corcoran Equations (1988)

5.3.2.1.21 Walser et al. Equations (1993)

5.3.2.1.22 Agarwal and Nicar Equations (1994)

5.3.2.1.23 Nankivell et al. Equations (1995)

5.3.2.1.24 Nankivell et al. Equations (SPK Recipients, 1995)

5.3.2.1.25 Toto et al. Equations (1997)

5.3.2.1.26 Nguyen et al. Equation (1997)

5.3.2.1.27 Baracskay et al. Equations (1997)

5.3.2.1.28 Levey et al. Equations (1999)

5.3.2.1.29 Levey et al. Equations (2000)

5.3.2.1.30 Rule et al. Equation (2004)

5.3.2.1.31 Levey et al. Equations (2006)

5.3.2.1.32 Ma et al. Equations (2006)

5.3.2.1.33 Björk et al. Equations (2007)

5.3.2.1.34 Imai et al. (2007)

5.3.2.1.35 Levey et al. Equations (2009)

5.3.2.1.36 Matsuo et al. (2009)

5.3.2.1.37 Schwartz et al. (2009)

5.3.2.1.38 Horio et al. Equations (2010)

5.3.2.1.39 Praditpornsilpa et al. (2011)

5.3.2.1.40 Alvarez-Gregori (2011)

5.3.2.1.41 Schaeffner et al Equations (2012)

5.3.2.1.42 Pottel et al. (2016)

5.3.2.1.43 Jalalonmuhali et al. Equations (2017)

5.3.2.1.44 Björk et al. Equations ( 2018)

5.3.2.1.45 European Kidney Function Consortium (EKFC) Equations (2021)

5.3.2.1.46 Mekonnen et al Equations (2025)

5.4 Limitations in Predicting Creatinine (Cr) Clearance from Serum Creatinine

5.4.1 Demographic Factors

5.4.1.1 Age-Related Influences

5.4.1.2 Ethnicity and Race

5.4.1.3 Diet and Lifestyle Factor Affecting Creatinine Generations

5.4.1.3.1 Vegetarian Diet

5.4.1.3.2 High Protein Diet

5.4.1.4 Physical Activity and Bed Rest

5.4.1.4.1 Physical Activity

5.4.1.4.2 Bed Rest

5.4.2 Clinical Status

I. Conditions Affecting Creatinine Production

5.4.2.1 Muscle-Wasting Diseases

5.4.2.2 Liver Diseases

5.4.2.3 Protein-Energy Wasting and Malnutrition

5.4.2.4 Amputation or Paralysis

5.4.2.5 Hypothyroidism

5.4.2.6 Hyperthyroidism

II.     Conditions Affecting Renal Handling of Creatinine

5.4.2.7 CKD and AKI Continuum

5.4.2.7.1 CKD Increases Susceptibility to AKI

5.4.2.7.2 AKI Accelerates CKD Progression

5.4.2.7.3 Clinical Implications and Diagnostic Challenges

5.4.2.8 Glomerulonephritis

5.4.2.8.1 Classification and Pathogenesis

5.4.2.8.2 Clinical Manifestations

5.4.2.8.3    Renal Function and Laboratory Findings

5.4.2.9 Tubulointerstitial Nephritis

5.4.2.10 Obstructive Uropathy

5.4.2.11 Renal Artery Stenosis

5.4.2.12 Renal Vein Thrombosis

5.4.2.13 Multiple Myeloma

III. Conditions Altering Creatinine Secretion or Assay Interference

5.4.2.14 Diabetic Nephropathy

5.4.2.15 Systemic Vasculitis

5.4.2.16 Drugs Influencing Serum Creatinine and/or Clearance

5.4.2.16.1 Trimethoprim (TMP)

5.4.2.16.2 Cimetidine

5.4.2.16.3 Cobicistat

5.4.2.16.4 Dolutegravir

5.4.2.16.5 Fenofibrate

5.4.2.16.6 Glucocorticoids

5.4.2.16.7 Cephalosporins

5.4.2.16.8 Ketone Bodies

5.4.2.16.9 Methyldopa

5.4.2.17 Jaundice/Hyperbilirubinemia

IV. Conditions affecting volume, TBW, or hemodynamics

5.4.2.18 Heart failure

5.4.2.19 Sepsis

5.4.2.20 Dehydration/volume depletion

5.4.2.21 Nephrotic syndrome

V. Other systemic or inflammatory conditions

5.4.2.23 Systemic Lupus Erythematosus (SLE) and Renal Function Assessment

5.4.2.24     Rhabdomyolysis and Renal Function Assessment

5.4.2.25     Cancer-Related Cachexia and Renal Function Assessment

5.4.2.26     Critical Illness and Prolonged Bed rest

5.4.2.27     Unspecified Population Traits

5.4.2.27.1  Comparative Studies of GFR Estimation Equations

5.4.2.27.2  Implications for Equation Selection and Model Development

Chapter 6.  Creatine (CR) and Creatinine (Cr) Analytical Methodologies

6.1 Introduction

6.2 Colorimetric Assays

6.2.1 Jaffe Reaction

6.2.2 Determination of Creatinine (Cr) in Biological Samples Using Jaffe Reaction

6.2.2.1                   Jaffe Reaction Interfering Chromogens

6.2.2.1.1    Endogenous Chromogens

6.2.2.1.2    Exogenous Chromogens

6.2.2.1.3    Mechanistic Categories of Jaffe Interferences

6.3 Established Enzymatic Methods for Creatinine Measurement

6.3.1 Standard Cascade

6.3.2 Creatinine Deiminase-Based Enzyme

6.3.3 Creatinine Amidohydrolase

6.3.4 Enzymatic Methods with Colorimetric Endpoints

6.3.5 Enzyme Immobilization Strategies Used for Creatininase -based and Creatinine Deiminase-based Biosensors

6.3.6 Comparison of Amperometric vs. Potentiometric Biosensors for creatinine

6.3.7 Limitations of Cascade Enzyme Systems and Amperometric Biosensors

6.3.8 Limitations of Creatinine Deiminase-Based Methods and Potentiometric Biosensors

6.4 Isotope Dilution Gas Chromatography-Mass Spectrometry (ID-GC/MS)

6.5 High-Performance Liquid Chromatography (HPLC)

6.6 Chemical Ionization Mass Spectrometry

6.7 Micellar Electrokinetic Chromatography (MEKC)

6.8 Analytical Methods for Measuring Creatine (CR) in Biological Samples

References

Chapter 7.  Creatine Supplement and Co-Supplements

Dosing Regimen, Bioavailability, Influence of Gender and Diet

7.1 Background

7.2 Prominent Creatine Types and Their Characteristics

7.2.1 Creatine Monohydrate

7.2.2 Creatine Hydrochloride

7.2.3 Buffered Creatine (Kre-Alkalyn®)

7.2.4 Creatine Nitrate

7.2.5 Creatine Magnesium Chelate

7.2.6 Creatine Ethyl Ester

7.2.7 Creatine Ethyl Ester Malate

7.2.8 Liquid Creatine

7.2.9 Creatine Citrate

7.2.10 Creatine Gluconate

7.3 Supplements Commonly Used Alongside Creatine

7.3.1 Creatinine as Supplement

7.3.2 β-Hydroxy-β-Methylbutyrate (HMB)

7.3.2.1 Synergic Relationship Between Creatine and HMB

7.3.3 Creatine Uptake Enhancers and Synergists

7.3.3.1 Carbohydrates

7.3.3.2 Alpha-lipoic Acid (ALA)

7.3.3.3 Sodium

7.3.3.4 Magnesium

7.3.4 Creatine Performance and Recovery Stack

7.3.4.1 Beta-Alanine

7.3.4.2 Branched-Chain Amino Acids (BCAAs)

7.3.4.3 Citrulline Malate

7.3.4.4 Taurine

7.3.5 Cognitive and Neuroprotective Pairing

7.3.5.1 Choline

7.3.5.2 Omega-3 Fatty Acids

7.3.5.3 Coenzyme Q10

7.3.6 Metabolic and Mitochondrial Enhancers

7.3.6.1 Ribose

7.3.6.2 Nicotinamide Riboside

7.4 Absorption and Bioavailability of Creatine Supplements

7.5 Dosing Regimen

7.5.1 More Realistic Dosing Approaches for Creatine Supplement

7.5.2 Vegetarian Versus Omnivores - Creatine Response

7.5.3 Gender-Specific Adaptation in Creatine Metabolism and Performance

References

Chapter 8.  Potential Therapeutic Values of Creatine Supplements in Selected Disease States

8.1 Background: Creatine as a Theranostic Agent

8.1.1 Potential Therapeutic Values of Creatine Supplements in Selected Disease States

8.2 Overview of Current Pharmacology of Creatine Supplement

8.2.1 Current Applications and Effects

8.2.2 Distribution and Storage of Creatine in the Body

8.2.3 Role of the Creatine Transporter (SLC6A8)

8.2.4 Muscle Augmentation and the Role of Creatine

8.2.5 Creatine’s Role and Application in Neurological and Neurodegenerative Disorders

8.2.6 Creatine (CR) Deficiency Syndromes (CDS)

8.2.6.1 AGAT Deficiency

8.2.6.2 GAMT Deficiency

8.2.6.2.1 Importance of Early Detection and Treatment

8.2.6.3 Creatine and SLC6A8 Deficiency

8.2.7 Creatine Supplementation and Parkinson’s Disease

8.2.8 Creatine and Creatinine Use in Amyotrophic Lateral Sclerosis (ALS)

8.2.9 Creatine Supplementation and Traumatic Brain Injury (TBI), Concussion, and Mild Traumatic Brain Injury (mTBI)

8.2.9.1 Classification and Symptoms of TBI

8.2.9.2 Creatine Metabolism and TBI Pathophysiology

8.2.9.3 Creatine Supplementation: Potential Therapeutic Role

8.3 Musculoskeletal and Metabolic Conditions

8.3.1 Creatine Supplementation in Sarcopenia and Muscle Atrophy

8.4 Cardiometabolic, Systemic Disorders, and Pregnancy

8.4.1 Creatine Supplementation in Type 2 Diabetes

8.4.2 Creatine Supplementation in Heart Failure

8.4.2.1 Mechanistic Insights and Biomarker Evaluation

8.4.2.2 Clinical Trials and Functional Outcomes

8.4.2.3 Anti-Inflammatory and Endothelial Effects

8.4.2.4 Vascular Function and Metabolic Markers

8.4.3 Creatine Supplementation in Pregnancy

8.4.3.1 Overview and Safety Considerations

8.4.3.2 Creatine’s Potential Functions During Pregnancy

8.4.3.3 Maternal Creatine Status and Pregnancy Outcomes

8.4.3.4 Animal Model Insights on Creatine Supplementation

8.4.3.5 Neuroprotective Potential and Clinical Implications

8.4.3.6 Creatine Across the Female Lifespan

8.5 Oncology and Immunomodulation

8.5.1 Creatine Supplementation for Cancer Patients and Cancer Survivors

8.5.1.1 Mechanistic Rationale and Clinical Evidence

8.5.1.2 Epidemiological Insights on Dietary Creatine and Cancer Risk

8.5.1.3 Clinical Trials in Oncology

8.5.1.4 Systematic Reviews and Context-Dependent Effects

8.5.1.5 Creatine’s Dual Role in Cancer Biology and Immunology

8.5.1.6 Emerging Clinical Trials: Resistance Training and Supplementation

8.5.2 Antioxidant and Anti-inflammatory Properties of Creatine

8.5.2.1 Direct Antioxidant Actions

8.5.2.2 Immunomodulatory Effects

8.5.2.3 Effects on Oxidative Stress and Inflammation in Exercise

8.5.2.4 Creatine Supplementation in Prenatal and Pediatric Inflammation

8.5.2.5 Geroprotective Effects and Cellular Senescence

8.5.2.6 Summary of Mechanisms

References

Chapter 9.  Side Effects of Orally Administered Exogenous Creatine

9.1 General Overview

9.1.1 Commonly Reported Side Effects

9.1.1.1 Renal and Metabolic Effects

9.1.1.2 Fluid Balance and Weight Changes

9.1.1.3 Musculoskeletal Concerns

9.1.1.4 Neurological and Cognitive Effects

9.1.1.5 Gastrointestinal Disturbances

9.1.1.6 Dermatological and Other Effects

9.1.2 Considerations for Special Populations

9.1.3 Mitigation Strategies

9.1.4 Consensus Statements and Recommendations

9.2 Organ/Mechanism Specific Adverse Effects

9.2.1 Creatine Supplement and Renal Function

9.2.2 Creatine Supplement and Hepatic Function

9.2.3 Creatine Supplement and Muscle Damage

9.2.3.1 Effects on Physical Performance

9.2.3.2 Muscle Recovery and Damage

9.2.3.3 Mechanisms of Action

9.2.3.4 Safety Profile and Side Effects

9.2.3.5 Limitations of the Review

9.2.4 Creatine Supplement and Overall Safety

9.2.5 Creatine Supplement and Glycemic Control, Insulin Sensitivity, and Glucose Metabolism

9.2.6 Creatine Supplementation and Anterior Compartment Pressure

9.2.7 Evidence-Based Overview of the Potential Side Effects of Creatine

References

Chapter 10. Exogenous Creatinine Supplement - Clinical Application of Creatinine Clearance

10.1     Introduction

10.2     Anti-inflammatory, Immunomodulatory and Antioxidant Action of Creatinine

10.3     Diagnostic and Clinical Uses of Creatinine

10.3.1 Renal Function Assessment

10.3.2 Drug Dosing Adjustment and Toxicity Monitoring

10.4     Other Applications of Creatinine

10.4.1 Nephrotoxicity Surveillance 10.4.2                Adjustment for Urine Concentration Variability 10.4.3                Nutritional and Muscle Mass Estimation 10.4.4                Creatinine Kinetics in Critical Care 10.4.5                Creatinine in Artificial Intelligence and Predictive Modeling 10.4.6                Isotope-Labeled Creatinine in Research 10.4.7                Dynamic Creatinine Kinetics in Hospitalized Patients 10.4.8                Comparative Renal Biomarkers 10.4.9                Precision Nephrology and Kidney Atlas Projects 10.4.10 Creatinine in Urine Normalization and Exposure Studies 10.4.11 Emerging Concepts

References

Addendum

Biography

Mehdi Boroujerdi received his Ph.D. in pharmaceutics and pharmacokinetics with minor in Biochemistry from the University of North Carolina at Chapel Hill in 1978. He completed his postdoctoral training at the National Institute of Health, National Institute of Environmental Health Sciences at Research Triangle Park. He served as the professor of pharmaceutics/pharmacokinetics with tenure at Northeastern University, Boston, MA (1982–2002); professor of pharmaceutics and pharmacokinetics at the MCPHS University, School of Pharmacy, Boston, MA (2002–2005); professor of pharmaceutical sciences with tenure at the Albany College of Pharmacy and Health Sciences, Albany, New York (2005–2015); and professor of pharmaceutical sciences with tenure at the College of Health Sciences, University of Massachusetts, Lowell, MA (2015–2017).

Boroujerdi has also served as Dean of School of Pharmacy at Bouvé College of Health Sciences at Northeastern University (1988–1999); as Dean of School of Pharmacy-Boston at MCPHS University (2002–2005); as Dean of Pharmacy and Vice President for Academic Affairs, Provost, at the Albany College of Pharmacy and Health Sciences (2006–2012); and Founding Dean of School of Pharmacy and Pharmaceutical Sciences at the College of Health Sciences, University of Massachusetts at Lowell (2015–2017). He also served as the Dean of Research and Graduate Studies at MCPHS (2003–2005), and Director of Graduate Programs in Biomedical Sciences at Northeastern University (1988–1999).

Boroujerdi has to his credit 112 peer-reviewed publications, and he is the sole author of three books: Pharmacokinetics, Principles and Applications (McGraw Hill, 2002), Pharmacokinetics and Toxicokinetics (CRC Publications, 2015), and Handbook of Pharmacokinetics and Toxicokinetics (CRC Publications, 2023). He has trained many graduate and undergraduate students through his research programs focused on pharmacokinetics and toxicodynamics of anticancer drugs, carcinogenesis, and efflux proteins.

He also served as a consultant to five pharmaceutical industries.

As a professor, he taught graduate courses in advanced pharmacokinetics and biopharmaceutics, drug metabolism, advanced pharmaceutics, and drug delivery systems; his teaching of undergraduate courses included drug discovery and development, biopharmaceutics and pharmacokinetics, physical pharmacy and pharmaceutics, and pharmacokinetics in disease states.