Manupat Lohitnavy

• PhD (Environmental Health; Toxicology)
• Managing Director at Naresuan University

Psilocybin is an active alkaloid found in magic mushrooms (Psilocybe cubensis). It is classified as a Class I Psychoactive Substance due to its psychoactive properties. Recent research has suggested that psilocybin holds potential for treating major depressive disorder. The objective of this study was to develop a physiologically based pharmacokine...

Importance Dapsone-induced hypersensitivity syndrome (DHS) is a life-threatening adverse drug reaction. Based on available epidemiologic studies, HLA genotypes may play an important role in DHS. Objective To assess the association between HLA-B*1301 and dapsone-induced cutaneous adverse drug reactions (cADRs). Data Sources Human studies investiga...

Smoking and asbestos exposure are important risks for lung cancer. Several epidemiological studies have linked asbestos exposure and smoking to lung cancer. To reconcile and unify these results, we conducted a systematic review and meta-analysis to provide a quantitative estimate of the increased risk of lung cancer associated with asbestos exposur...

Background and Objective∆9-Tetrahydrocannabinol (THC) exhibits several therapeutic effects, such as analgesics, anti-emetic, antispastic, and muscle relaxation properties. Knowledge concerning THC disposition in target organs is crucial for THC therapy. The objective of this study was to develop a physiologically-based pharmacokinetic (PBPK) model...

To reconcile and unify available results regarding paraquat exposure and Parkinson’s disease (PD), we conducted a systematic review and meta-analysis to provide a quantitative estimate of the risk of PD associated with paraquat exposure. Six scientific databases including PubMed, Cochrane libraries, EMBASE, Scopus, ISI Web of Knowledge, and TOXLINE...

Background and Objective Tacrolimus is a narrow therapeutic index drug with high pharmacokinetic variability, and several tacrolimus population pharmacokinetic (PopPK) models were developed to guide individualized drug dosing. These models, however, may not perform well in other clinical settings. Therefore, we aimed to assess the predictive abilit...

Background : Psilocybin (PB) is a psychoactive compound commonly found in magic mushroom ( Psilocybe cubensis ) . PB is quickly converted by the body to psilocin (PI), which has a psychedelic effect through the activation of the 5 - HT 2A receptor in the brain. The objective of this study is to develop a physiologically based pharmacokinetic (PBPK)...

Many recent studies reported coronavirus point-of-care tests (POCTs) based on isothermal amplification. However, the performances of these tests have not been systematically evaluated. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy was used as a guideline for conducting this systematic review. We searched peer-reviewed and pre...

Mitragynine is a major psychoactive alkaloid in leaves of kratom (Mitragyna speciosa Korth.). To understand its disposition in organs, this study aimed to develop a physiologically based pharmacokinetic (PBPK) model that predicts mitragynine concentrations in plasma and organ of interests in rats and humans. The PBPK model consisted of six organ co...

Adequate postoperative pain control with minimal side effects is necessary for patients undergoing total knee arthroplasty (TKA). Ketorolac is a frequently used nonsteroidal anti-inflammatory drug due to its excellent disposition in all administration routes; however, it possesses an “analgesic ceiling,” which means that higher doses of the drug ha...

Carbamazepine is a narrow therapeutic index drug requiring therapeutic drug monitoring, while population pharmacokinetics is an approach that can aid individualized dosing regimens and to date, several population pharmacokinetic studies of carbamazepine have been conducted. This systematic review aims to summarize the factors influencing carbamazep...

Many recent studies reported coronavirus point of care tests (POCTs) based on isothermal amplification. However, the performances of these tests have not been systematically evaluated. We searched databases for studies that provide data to calculate sensitivity, specificity and diagnostic odds ratio (DOR). We included 43 studies on 5204 specimens....

Hydrogen cyanide (HCN) is volatile and highly toxic with acute and chronic effects on humans. Gaseous HCN enters the atmosphere from natural processes or industrial activities, which lead to human exposure. Effective intervention in cases of HCN inhalation requires an efficient diagnostic tool. The existing physiologically based pharmacokinetic (PB...

Serious cutaneous adverse drug reactions [i.e., SJS/TEN with severe ocular complications (SOC)] associated with cold medicine (CM) were reported in several studies. To assess the risks of CM-induced SJS/TEN with SOC, systematic review and meta-analysis were employed. Studies investigating associations between HLA genotypes and CM-induced SJS/TEN wi...

Background and Objective There has been an increase in the use of cannabis. Delta-9-tetrahydrocannabinol, (THC) is the major psychoactive compound, which has both therapeutic and narcotic effects. THC pharmacokinetics are important for designing optimal dosing regimens, and physiologically-based pharmacokinetic (PBPK) models are used to predict a c...

Associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity have been reported. To consolidate the results from all available reports in scientific databases, systematic review and meta-analysis techniques were used to quantify these associations. Studies investigating associations between HLA-DRB1*07:01 and lapatinib-induced hepatotox...

Methazolamide-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are life-threatening adverse drug reactions. Based on previous studies, HLA genotypes may play an important role in methazolamide-induced SJS/TEN. Therefore, to identify the associations between HLA genotypes and methazolamide-induced cutaneous adverse drug reac...

Background and objective: Kratom (Mitragyna speciosa) is a tropical tree found in southern Thailand and northern states of the Malay Peninsula. Kratom is commercially available and used as an alternative to treat opioid withdrawal. Mitragynine is the major indole alkaloid found in kratom leaves. This review aimed to summarize available pharmacokin...

Cyanogenic glycosides (CGs) are commonly found in some edible plants and seeds. After ingestion, CGs can release toxic hydrogen cyanide (HCN) in humans. At present, unfortunately, there is no tool capable of predicting the cyanide concentration in human blood and organs following oral administration of CG-containing food. The aim of this study was...

Objective: To assess the performance of the population pharmacokinetic model by Yukawa et al. in predicting lithium levels at the steady state in Thai bipolar patients, comparing with that of the traditional method. Method: The study retrospectively collected the data from 140 Thai patients with 85 female and average weight and age of 36.3 years an...

Objective To evaluate external predictability of a population pharmacokinetic model of valproic acid in Thai patients with mania to ensure its appropriateness for use in other clinical settings. Methods The published population pharmacokinetic model was evaluated for its predictive ability (at both individual and population levels) and its precisi...

Purpose: To systematically review and quantitatively synthesize associations between HLA genotypes and oxcarbazepine-induced cutaneous adverse drug reactions (OXC-cADRs), including Stevens-Johnson syndrome (SJS) and maculopapular rash. Methods: Studies investigating associations between HLA genotypes and OXC-cADRs were systematically searched ir...

Background: Clopidogrel is a thienopryridine antiplatelet agent commonly used in the management of cardiovascular diseases. Clopidogrel is metabolized by hepatic CYP2C19 and CYP2B6, therefore, co-administration of clopidogrel and CYP2C19 inhibitors can alter pharmacokinetics of clopidogrel. Omeprazole is a proton pump inhibitor used for decreasing...

An updated physiologically-based pharmacokinetic (PBPK) model of methotrexate (MTX) was built based on an earlier model developed by Bischoff et al. (1971). MTX has been known to be a substrate of multidrug-resistance-associated protein 2 (Mrp2). A three-dimensional quantitative structure-activity relationship model (3D-QSAR) of Mrp2 was developed...

Paraquat (N, N'-dimethyl-4,4'-bipyridium dichloride) is a potent and widely used herbicide in agricultural countries, including Thailand. The presence of this chemical in the body can lead to toxic effects in the liver, kidney, and lung. Pulmonary toxicity has been identified as the main cause of acute toxicity in animals and humans. Chronic exposu...

The mechanism of drug-drug interaction between saquinavir, a protease inhibitor used effectively for HIV/AIDS treatment, and itraconazole, an azole antifungal agent, is hypothesized to involve competitive inhibition at CYP3A4 enzyme, an important drug metabolizing enzyme in humans. The resulting interaction between these CYP3A4 substrates can be ut...

BACKGROUND: Concomitant use of simvastatin, a HMG-CoA reductase inhibitor, with a potent CYP3A4 inhibitor, itraconazole, can result in a serious drug-drug interaction induced severe adverse event, rhabdomyolysis. Even though pharmacokinetic data regarding such interaction are available, they cannot be used for quantitative prediction. For this reas...

This study aimed to systematically review and quantitatively synthesize the association between HLA-B*5701 and abacavir-induced hypersensitivity reaction (ABC-HSR). We searched for studies that investigated the association between HLA-B genotype and ABC-HSR and provided information about the frequency of carriers of HLA-B genotypes among cases and...

Ritonavir-boosted lopinavir (LPV/r) has been recommended as an alternative regimen for HIV-naive patients who cannot tolerate nevirapine (NVP) and/or efavirenz (EFV). Although combinations of ritonavir and lopinavir have shown higher plasma concentration level of LPV in clinical settings, dosage adjustment is still required to maintain an adequate...

Verapamil is a calcium channel blocker commonly used in treatments of hypertension. Verapamil and its active metabolite, norverapamil, are known to be CYP3A4 inhibitors. Co-administration of verapamil with CYP3A4 substrates can alter the pharmacokinetics of the substrates. Simvastatin, a commonly used HMG-CoA reductase inhibitor for the treatment o...

Simvastatin, a commonly used HMG-CoA reductase inhibitor, is extensively metabolized by CYP3A4. Therefore, co-administration of simvastatin and CYP3A4 inhibitor can affect simvastatin pharmacokinetics. Nelfinavir, a protease inhibitor, and its major metabolite (M8) are known to be potent CYP3A4 inhibitors. When simvastatin and nelfinavir are co-adm...

Simvastatin is a HMG-CoA reductase Inhibitor and a substrate of CYP3A4. Clarithromycin is a commonly used macrolide antibiotics and a potent inhibitor of CYP3A4. When co-administered with simvastatin, clarithromycin can significantly increase simvastatin plasma concentration levels, thereby, increase the risk of rhabdomyolysis. At present, pharmaco...

Objectives: This study aimed to systematically review and quantitatively synthesize an association between HLA genotype and stavudine-induced lipodystrophy in HIV patients. Design: Systematic review and meta-analysis. Methods: A systematic search for studies that investigated the association between HLA genotype and stavudine-induced lipodystrophy...

Background: Previous studies have demonstrated that grapefruit juice increased the bioavailability of cyclosporine;however, the results from the literature are inconsistent. Other citrus fruits such as pomelo or orange juice had variable effects on the bioavailability of cyclosporine.Objective: To assess the effect of grapefruit juice and other typ...

Importance: The US Food and Drug Administration recommends screening for the HLA-B*1502 allele before initiation of carbamazepine therapy in patients of Asian ancestry, but there remains unclear evidence of a relationship between HLA-B*1502 and Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) among carbamazepine users, especiall...

Background: Lopinavir is a highly potent protease inhibitors commonly used in treatment of HIV infection. The drug has a very low bioavailability due to a rapid metabolism by cytochrome P450 3A (CYP3A) isoenzyme. We aimed to develop a biologically relevant pharmacokinetic model of lopinavir with a description of a CYP3A4-mediated first pass metabo...

OBJECTIVES: Despite some studies suggesting a possible association between human leukocyte antigen (HLA), HLA-B*1502 and carbamazepine induced Stevens - Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its magnitude remain inconclusive. This study aims to systematically review and quantitatively synthesiz...

Despite some studies suggesting a possible association between human leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its magnitude remain inconclusive. This study aims to systematically review and meta-analyze the association between HLA-B*580...

MeHg and PCB exposure to lactating mice were analyzed and a physiologically-based pharmacokinetic (PBPK) model was developed to describe the lactational transfer of MeHg in mice. The influence of albumin on the lactational transfer of MeHg was incorporated into the PBPK model. Experimental results with lactating mice and their pups showed that co-e...

3,3',4,4',5'-Pentachlorobiphenyl (PCB126) is a carcinogenic environmental pollutant and its toxicity is mediated through binding with aryl hydrocarbon receptor (AhR). Earlier, we found that PCB126 treated F344 rats had 110-400 times higher PCB126 concentration in the liver than in the fat. Protein binding was suspected to be a major factor for the...

PBPK modeling has been increasingly applied in chemical risk assessment for dose, route, and species extrapolation. The use of PBPK modeling was explored in deriving toxicity reference values for 1,1,1-trichloroethane (1,1,1-TCE). This effort involved a 5-step process: (i) reconstruction of several published PBPK models for 1,1,1-TCE in the rat and...

The objectives of this study were twofold: (1) evaluating the carcinogenic potential of the mixture of two persistent environmental pollutants, hexachlorobenzene (HCB) and 3,3',4,4',5-pentachlorobiphenyl (PCB 126), in an initiation-promotion bioassay involving the development of pi glutathione S-transferase (GST-P) liver foci, and (2) analyzing the...

Chlordecone (CD) and mirex (M) differ by a single carbonyl group in CD in place of two chlorines in M. Although both compounds are lipophilic, their tissue distributions differ markedly: CD concentrations are highest in liver; M concentrations are highest in fat. We used tissue time course data in rats from our laboratory for CD and M and literatur...

Physiologically based pharmacokinetic (PBPK) modeling is generally used for describing xenobiotic disposition in animals and humans with normal physiological conditions. We describe here an updated PBPK model for hexachlorobenzene (HCB) in male F344 rats with the incorporation of pathophysiological conditions. Two more features contribute to the di...

To investigate the effects of antacid suspension on oral absorption of itraconazole. A randomized, open-labelled, two-period, crossover study with a 1-week washout period was conducted in 12 healthy Thai male volunteers. The participants were allocated in either treatment A or B in the first period. In treatment A, the volunteers were orally admini...

Studie zur Bioäquivalenz zweier Simva-statin-Tablettenformulierungen an gesunden thailändischen Probanden Die Bioäquivalenz zweier Simvastatin (CAS 79902-63-9)-Tablettenformulierungen à 10 mg – Vascor® als Testprodukt sowie eine handelsübliche Zubereitung als Referenzprodukt – wurde an 18 gesunden männlichen thailändischen Probanden untersucht. led...

The pharmacokinetic and relative bioavailability studies of 20-mg enalapril tablets, the test product manufactured by Biolab, Thailand compared to the reference product (Merck Sharp & Dohme, USA) was conducted in 14 healthy Thai male volunteers following a single dose, two-period, crossover design. Each subject received 20-mg enalapril tablets of b...

The objective of this study was to assess bioequivalence of 500-mg clarithromycin tablets in 24 healthy volunteers. In a randomized, single dose, fasting state, two-period, crossover study design with a 1-week washout period, each subject received a 500-mg clarithromycin tablet. Plasma samples were collected over a 24-h period after administration...

The objective of this study was to assess average bioequivalence of two immediate released tablet formulations of 500-mg clarithromycin tablets in 24 healthy Thai male volunteers. In a randomized, single dose, fasting state, two-period, crossover study design with a 1-week washout period, each subject received a 500-mg clarithromycin tablet. Plasma...

To evaluate the average bioequivalence of two formulations of 500 mg clarithromycin tablets in 24 healthy Thai male volunteers. In a randomized, single dose, fasting state, two-period, crossover study design with a 1-week washout period, each subject received a 500 mg clarithromycin tablet. Plasma samples were collected over a 24-h period after adm...

To assess the average bioequivalence of two formulations of 8-mg ondansetron tablets--test product (Unison Laboratories, Thailand) and reference product (Glaxo Wellcome, USA)--in 14 healthy Thai male volunteers. In a randomized, single dose, fasting, two-period, crossover study design with a 1-week washout period, each subject received an 8-mg onda...

The bioequivalence study of 5-mg enalapril tablets, Enaril (Biolab, Thailand) compared to Renitec (Merck Sharp & Dohme, USA) was conducted in 14 healthy Thai male volunteers following a single dose, two-period, crossover design. Each subject received 4 tablets of 5-mg enalapril tablets of both formulations with a 1-week washout period. Plasma sampl...