Interpretable machine learning model predicting immune checkpoint inhibitor-induced hypothyroidism: A retrospective cohort study.

Hypothyroidism is a known adverse event associated with the use of immune checkpoint inhibitors (ICIs) in cancer treatment. This study aimed to develop an interpretable machine learning (ML) model for individualized prediction of hypothyroidism in patients treated with ICIs. The retrospective cohort of patients treated with ICIs was from the First Affiliated Hospital of Ningbo University. ML methods applied include logistic regression (LR), random forest classifier (RFC), support vector machine (SVM), and extreme gradient boosting (XGBoost). The area under the receiver-operating characteristic curve (AUC) was the main evaluation metric used. Furthermore, the Shapley additive explanation (SHAP) was utilized to interpret the outcomes of the prediction model. A total of 458 patients were included in the study, with 59 patients (12.88%) observed to have developed hypothyroidism. Among the models utilized, XGBoost exhibited the highest predictive capability (AUC = 0.833). The Delong test and calibration curve indicated that XGBoost significantly outperformed the other models in prediction. The SHAP method revealed that thyroid-stimulating hormone (TSH) was the most influential predictor variable. The developed interpretable ML model holds potential for predicting the likelihood of hypothyroidism following ICI treatment in patients. ML technology offers new possibilities for predicting ICI-induced hypothyroidism, potentially providing more precise support for personalized treatment and risk management.

Fibroblast growth factor 20 ameliorates cardiac hypertrophy via activation ErbB2.

Fibroblast growth factor 20 (FGF20) is a member of the fibroblast growth factor family and involved in embryonic development and cardiac repair. This study aimed to explore the role of FGF20 in cardiac hypertrophy and the underlying molecular mechanisms. FGF20 improved cardiac hypertrophy in vivo and in vitro. Furthermore, FGF20 increased expression of erythroblastic leukemia viral oncogene homolog 2 (ErbB2), which was negatively correlated with expression of the cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). In addition, FGF20 effectively protected cardiomyocytes against apoptosis and oxidative stress. To further investigate whether protective effect of FGF20 is mediated by ErbB2, neonatal rat cardiomyocytes (NRCMs) were treated with lapatinib, an inhibitor of ErbB2. Lapatinib largely abrogated the anti-hypertrophic effect of FGF20, accompanied by increases in cardiomyocyte apoptosis and oxidative stress. In summary, this study reveals that FGF20 prevents cardiac hypertrophy by inhibiting apoptosis and oxidative stress via activating ErbB2 and may be a promising therapeutic strategy for cardiac hypertrophy.

Post-marketing safety of finerenone: a disproportionality analysis of the FDA adverse event reporting system.

BACKGROUND: Finerenone was approved for the treatment of type 2 diabetes patients with chronic kidney disease. However, the post-marketing safety of finerenone in the real world is unknown. METHODS: The quarterly reported data related to finerenone from the third quarter of 2021 to the second quarter of 2023 were collected by using the FAERS database. Two disproportionality analysis methods were estimated by using Reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN). RESULTS: A total of 1067 adverse events (AEs) were included. Twenty-four kinds of system organ classes (SOCs) were classified for the organs and systems involved and 39 AEs with significant safety signals were identified using ROR and BCPNN at the preferred terms (PTs) level. Most AEs originated from the United States, and the median time to onset of AEs was 13 days. Three hundred and fifty-one (55.5%) reported serious outcome. The proportion of medication combinations was 29.0%. The most commonly reported AEs were the glomerular filtration rate decreased. Safety signals have also been observed in new and unexpected AEs. CONCLUSION: The analysis of the AE signals may contribute to minimizing the risks associated with its use.

Mechanism Analysis of Selenium-Containing Compounds in Alleviating Spinal Cord Injury Based on Network Pharmacology and Molecular Docking Technology.

Spinal cord injury (SCI) is a severe traumatic condition in spinal surgery characterized by nerve damage in and below the injured area. Despite advancements in understanding the pathophysiology of SCI, effective clinical treatments remain elusive. Selenium compounds have become a research hotspot due to their diverse medicinal activities. Previously, our group synthesized a selenium-containing Compound 34# with significant anti-inflammatory activity. This study aimed to explore the anti-SCI effects of selenium-containing compounds using network pharmacology, molecular docking (MD), and ADMET methods. To identify SCI-related targets and those associated with 34#, GeneCards, NCBI, and SEA databases were employed. Eight overlapping targets were considered candidate targets, and molecular docking was performed using the PDB database and AutoDock software. The STRING database was used to obtain protein-protein interactions (PPI). Molecular dynamics simulation, MM/GBSA binding free energy score, and ADMET prediction were used to evaluate the potential targets and drug properties of 34#. Finally, experiments on NSC34 cells and mice were to verify the effects of 34# on SCI. Our results revealed eight candidate targets for 34# in the treatment of SCI. PPI and MD identified ADRB2 and HTR1F as the highest connectivity with 34#. ADMET analysis confirmed the low toxicity and safety of 34#. In vitro and in vivo models validated the anti-SCI effects. Our study elucidated candidate targets for alleviating SCI with 34#, explored PPI and target-related signaling pathways, and validated its anti-SCI effects. These findings enhance our understanding of 34#'s mechanism in treating SCI, positioning it as a potential candidate for SCI prevention.

Efficacy and action mechanisms of compound Shen Chan decoction on experimental models of atopic dermatitis.

Shen chan decoction (SCD) as a significant Traditional Chinese medicine (TCM) to treat atopic dermatitis (AD), but its mechanism of action has not been clarified, so we started the present study, first possible effects of SCD on AD were predicted using network pharmacology. Next, dinitrochlorobenzene was used to establish a mouse model of AD. After successful modelling, the SCD were administered intragastrically to treat the mice. Eventually, the KEGG pathway enrichment analysis indicated that SCD improved AD mainly through effects on inflammation and the gut microbiota. The experimental findings revealed that SCD treatment attenuated AD symptoms and downregulate the characteristic immune factors, namely IL-4, IL-6 and IgE. Moreover, it promoted a balance between Th1/Th2 cells. Furthermore, the itch signaling pathways involving H1R/PAR-2/TRPV1 were inhibited. The 16S rRNA sequencing results indicated that SCD administration influenced the Firmicutes/Bacteroidetes ratio at the phylum level by augmenting the relative proportions of Lactobacillaceae and Muribaculaceae at the family and genus levels, while decreasing the abundances of Lactococcus and Ruminococcus. These findings suggest that internal administration of SCD is an effective therapeutic approach for AD. We suggest that SCD may be an alternative therapy for the treatment of AD.Additionally, it could offer valuable insights into the pathogenesis of AD and the development of innovative therapeutic agents.

Abrocitinib-associated adverse events: a real-world pharmacovigilance study using the FAERS database.

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Janus kinase (JAK) modulates cytokines involved in AD pathophysiology, and JAK inhibitors have emerged as effective pharmacotherapeutic remedies for AD. Abrocitinib, an oral selective inhibitor of JAK1, is indicated for the management of moderate-to-severe AD. The current study evaluated the adverse events (AEs) associated with abrocitinib in a real-world setting. METHODS: To quantify the signals of abrocitinib-associated AEs, we used the US Food and Drug Administration Adverse Event Reporting System (FAERS) for this pharmacovigilance study with two established pharmacovigilance methods. RESULTS: A total of 1071 AEs of abrocitinib were investigated as the primary suspected from the FAERS to detect and characterize relevant safety signals. The analysis revealed 85 signals for abrocitinib. The most common AE for abrocitinib was drug ineffective. The signal strength of eczema herpeticum was 515.87 (277.80-957.98) and 510.59 (5148.65) and exhibited the highest strength for abrocitinib. Rare AEs such as aggravated condition, pruritus, and hypersensitivity were not listed on the label, and attention to these AEs is required. CONCLUSION: The analysis of the AE signals may provide support for clinical monitoring and risk identification of abrocitinib.

Fatty Liver, Statin Therapy, and the Risk of Hypertriglyceridemic Acute Pancreatitis: A Retrospective Study.

OBJECTIVES: Identifying patients with severe hypertriglyceridemia (HTG) who are prone to developing hypertriglyceridemic pancreatitis (HTGP) is essential for facilitating preventative interventions. This research aims to explore which part of the HTG patients is easy to develop into HTGP. MATERIALS AND METHODS: An observational cohort study was conducted in patients with serum triglycerides (TGs) ≥ 5.65 mmol/L. Propensity score matching (PSM) and logistic regression were used to adjust for potential confounding factors. Receiver operating characteristic (ROC) curves were applied to evaluate the predictive potential for HTGP. RESULTS: A total of 283 patients were included finally with a PSM cohort consisting of 55 HTGP matched with 77 non-HTGP. In multivariate logistic regression analysis, fatty liver (FL) (odds ratio, 2.535; P = 0.019) showed statistically significant association with HTGP, whereas statin use was correlated with a lower rate of HTGP (odds ratio, 0.203; P = 0.009). Finally, the ROC analysis showed that the TGs threshold thought to be causal of HTGP in patients with FL was significantly lower (9.31 vs 14.67 mmol/L) than that in patients without FL. CONCLUSIONS: Although with lower TGs levels, patients with FL are much more prone to generate HTGP, and our findings suggest a potential role of statin as protective agents against HTGP.

Characteristics of adverse drug reactions induced by flutamide and bicalutamide: a real-world pharmacovigilance study using FAERS.

BACKGROUND: Flutamide and bicalutamide are indicated for the management of prostate metastatic carcinoma. The current study evaluated the adverse drug reactions related to flutamide and bicalutamide in a real-world setting. METHODS: To quantify the signals of flutamide and bicalutamide associated adverse events (AEs), we used the US Food and Drug Administration Adverse Event Reporting System (FAERS) for this pharmacovigilance study using established pharmacovigilance methods. RESULTS: A total of 2711 AEs of flutamide were investigated as the primary suspected; 522 AEs were related to prostate cancer. A total of 4459 AEs were investigated as the primary suspected for bicalutamide; 2251 AEs were related to prostate cancer. The analysis demonstrated 29 signals for flutamide and 84 for bicalutamide. Liver function test was the most common AEs for flutamide, and malignant neoplasm progression was the most common for bicalutamide. The signal strength of Dementia Alzheimer's type was 26.53 (17.89-39.35) and 26.33 (607.34), which had the highest strength for flutamide. Anti-androgen withdrawal syndrome exhibited the strongest signal for bicalutamide. Generating awareness of rare AEs that were not listed on the label is critical. CONCLUSIONS: The analysis of the AE signals may provide support for prescribing flutamide and bicalutamide.

A study on molecular mechanism of Xihuang pill in the treatment of glioblastoma based on network pharmacology and validation in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pill has been utilized to treat cancer for more than three hundred years in China. The molecular mechanisms of Xihuang pill in treating glioblastoma remains unclear. AIM OF THE STUDY: This study aimed to explore the core molecular mechanisms of Xihuang pill in treating glioblastoma by an integrative pharmacology-based investigation. MATERIALS AND METHODS: The main active compounds of Xihuang pill were identified from TCMSP, BATMAN-TCM, TCMID and CNKI. Glioblastoma-related therapeutic targets were retrieved from GeneCards and UniProt. Subsequently, a protein-protein interaction (PPI) network analysis was constructed using STRING. GO and KEGG enrichment were performed to analyze the intersection targets between the active compounds of Xihuang pill and glioblastoma. Based on the above analysis, we built a CTP network. The in vitro and in vivo experiments were further performed to validate the crucial molecular targets of Xihuang pill for the treatment of glioblastoma. RESULTS: A total of sixty active compounds of Xihuang pill and ten potential targets related to glioblastoma were found. Based on topological analysis, fourteen ingredients were selected as the main active compounds, and MY11 might be the most important metabolite in Xihuang pill. PI3K/Akt signaling pathway and receptor tyrosine kinases were considered as crucial targets for Xihuang pill against glioblastoma through KEGG enrichment and CTP analysis. The present experiments indicated that Xihuang pill suppressed the activation of PI3K/Akt/mTOR signaling pathway in glioblastoma cells and mouse xenografts via modulating the expression of PTEN and Rheb proteins, the interaction between TSC2 and Rheb, and the production of PIP3. Meanwhile, after glioblastoma cells treatment with Xihuang pil, the release of IL-1ß, INF-γ was increased and the production of IL-10, TGF-ß1 was decreased in glioblastoma cells after incubated with Xihuang pill. In addition, the activation of the upstream positive modulators of PI3K/Akt/mTOR pathway including PDGF/PDGFR and FGF/FGFR signaling were down-regulated in glioblastoma cells and mouse xenografts after treatment with Xihuang pill. CONCLUSION: Taken together, Xihuang pill inhibiting glioblastoma cell growth might be partly through down-regulating the activation of PDGF/PDGFR or FGF/FGFR-PI3K/Akt/mTOR signaling axis and improving immuno-suppressive micro-environment of glioblastoma.

Research progress on desensitization of hypersensitivity reaction to iodinated contrast media. / ç¢˜é€ å½±å‰‚è¶ æ•ååº”æ‚£è€ è„±æ•æ²»ç–—çš„ç ”ç©¶è¿›å±•.

Desensitization therapy for iodinated contrast media (ICM) aims to induce drug tolerance in patients with a history of severe allergic reactions to ICM in a short time. Currently, there is no widely accepted consensus on inducing desensitization to avoid severe allergic responses to ICM. The clinically successful cases have shown that prophylactic use of antihistamines and glucocorticoids can increase the desensitization effect; repeatedly desensitizing and gradually increasing the dose can be conducive to establishing better tolerance to ICM. Most desensitization effects, including stress resistance, can endure 24-48 h. The mechanisms of desensitization therapy remain unclear, the initial dose, administration interval and dose gradient are largely based on clinical experiences and the reaction of patients. This article reviews the current research progress on ICM-related allergies, desensitization methods and related mechanisms, as well as the benefits and hazards of desensitization, to provide a reference for desensitization treatment of hypersensitivity to ICM .

Thyroid function analysis after roxadustat or erythropoietin treatment in patients with renal anemia: a cohort study.

PURPOSE: This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia. METHODS: The study involved 110 patients with renal anemia. Thyroid profile and baseline investigations were carried out for each patient. The patients were divided into two groups: 60 patients taking erythropoietin served as the control group (rHuEPO group) and 50 patients using roxadustat served as the experimental group (roxadustat group). RESULTS: The results indicated that there were no significant differences in serum total thyroxine (TT4), total triiodothyronine (TT3), free triiodothyronine (FT3), free thyroxine (FT4) or thyroid stimulating hormone (TSH) between the two groups at baseline. After treatment, TSH, FT3, and FT4 were significantly lower in the roxadustat group than in the rHuEPO group (p < 0.05). After adjusting for age, sex, dialysis modality, thyroid nodules and causes of kidney disease, Cox regression showed that roxadustat was an independent influencing factor on thyroid dysfunction (HR 3.37; 95% CI 1.94-5.87; p < 0.001). After 12 months of follow-up, the incidence of thyroid dysfunction was higher in the roxadustat group than in the rHuEPO group (log-rank p < 0.001). CONCLUSION: Roxadustat may lead to a higher risk of thyroid dysfunction, including low TSH, FT3 and FT4, than rHuEPO in patients with renal anemia.

Metformin alleviates ethanol-induced cardiomyocyte injury by activating AKT/Nrf2 signaling in an ErbB2-dependent manner.

BACKGROUND: Metformin, a first-line oral anti-diabetic drug, has recently been reported to exert protective effect on various cardiovascular diseases. However, the potential role of metformin in ethanol-induced cardiomyocyte injury is still unknown. Therefore, this study was aimed to investigate the effect of metformin on ethanol-induced cardiomyocyte injury and its underlying mechanism. METHODS AND RESULTS: H9c2 cardiomyocytes were exposed to ethanol for 24 h to establish an ethanol-induced cardiomyocyte injury model, and followed by treatment with metformin in the presence or absence of Lapatinib (an ErbB2 inhibition). CCK8 and LDH assays demonstrated that metformin improved cell viability in cardiomyocytes exposed to ethanol. Furthermore, metformin suppressed cardiomyocyte apoptosis and reduced the expressions of apoptosis-related proteins (Bax and C-CAS-3). In addition, our results showed that metformin activated the AKT/Nrf2 pathway, and then promoted Nrf2 nuclear translocation and the transcription of its downstream antioxidant genes (HO-1, CAT and SOD2), thereby inhibiting oxidative stress. Interestingly, we found that ErbB2 protein expression was significantly inhibited in ethanol-treated cardiomyocytes, which was markedly reversed by metformin. In contrast, Lapatinib largely abrogated the activation of AKT/Nrf2 signaling by metformin, accompanied by the increases in oxidative stress and cardiomyocyte apoptosis, indicating that metformin prevented ethanol-induced cardiomyocyte injury in an ErbB2-dependent manner. CONCLUSION: In summary, our study provides the first evidence that metformin protects cardiomyocyte against ethanol-induced oxidative stress and apoptosis by activating ErbB2-mediated AKT/Nrf2 signaling. Thus, metformin may be a potential novel treatment approach for alcoholic cardiomyopathy.

Haemolytic anaemia induced by flutamide: a case report.

Flutamide-induced haemolytic anaemia is rare but can be fatal. We describe the case of an 88-year-old man with prostatic carcinoma who, in addition to clinically obvious jaundice, developed haemolytic anaemia after undergoing treatment with flutamide for 5 days. When flutamide was replaced with temporary adrenocortical hormone treatment and blood transfusion, the blood indices and liver function of the patient improved gradually. We emphasise the need for routine monitoring of blood counts for patients undergoing flutamide treatment, and highlight the importance of discontinuing flutamide immediately when haemolytic anaemia occurs.

Factors affecting voriconazole concentration to dose ratio changes according to route of administration.

BACKGROUND: Voriconazole (VRCZ) is commonly used as oral and intravenous (IV) formulations. Few studies have comprehensively analysed the variation factors for the weight-corrected VRCZ serum concentration/dose (C/D) ratio based on the administration route. We retrospectively investigated the risk factors that influence the VRCZ C/D ratio in patients treated with oral or IV formulations. METHODS: A total of 325 patients were divided into two groups (IV and oral groups). Propensity score matching was performed and linear regression analyses were used to identify the risk factors that affect the VRCZ C/D ratio according to the administration route. Receiver operating characteristic (ROC) curves were also used to assess the predictive potential for VRCZ trough concentration >5 µg/mL. RESULTS: The VRCZ C/D ratio in the oral group was significantly lower than that in the IV group (p<0.001). Propensity score matching resulted in 65 in the IV group matched with 65 in the oral group. Multivariate analysis showed that age (p=0.039), aspartate aminotransferase (AST) (p=0.016) and total bilirubin (TBIL) (p=0.041) levels were independent influencing factors of the VRCZ C/D ratio in the oral group. ROC curves showed that the predicted probability of combined age, AST and TBIL had maximal area under the curve (AUC) of 0.901 for VRCZ trough level >5 µg/mL. Meanwhile, the ratio of TBIL (p=0.005) and single dose (p=0.015) were independent factors in the IV group with ROCAUC of 0.781. CONCLUSIONS: To obtain optimal VRCZ efficacy and safety, dose adjustment is required based on multiple factors that may cause the observed difference in the VRCZ C/D ratio and trough levels between oral and IV administration.

Re-exposure to iodinated contrast media in two patients with prior severe hypersensitivity reaction.

OBJECTIVE: Most allergic reactions to iodinated contrast media can be managed using a pre-treatment protocol involving corticosteroids and antihistamines. However, under certain circumstances, patients may experience severe allergic symptoms despite pre-treatment. CASE REPORT: Two Chinese men with a history of severe contrast allergy and unstable angina underwent a desensitization protocol that allowed for successful percutaneous coronary intervention. CONCLUSION: Rapid desensitization is an effective and safe strategy that may allow other patients with similar allergies to successfully undergo angiography that requires the use of radiocontrast media.

Influence of cerebrospinal fluid drainage and other variables on the plasma vancomycin trough levels in postoperative neurosurgical patients.

BACKGROUND: Therapeutic drug monitoring (TDM) aims to minimise the clinical impact of vancomycin (VCM) pharmacokinetic variability. However, TDM data are limited among specific patient populations, including postoperative neurosurgical populations. The objective of this study was to retrospectively investigate the influence of cerebrospinal fluid (CSF) drainage and other factors on the serum trough concentrations of VCM. METHODS: We analysed 154 patients who had been hospitalised in the neurosurgical ward and received intravenous infusions of VCM. We compared the daily doses of VCM, serum VCM concentrations, and serum concentration/dose ratio (C/D ratio) between patients who underwent CSF drainage (drainage group) and controls (nondrainage group). In addition, we also elucidated other factors affecting the attainment of target concentrations. RESULTS: The patients in the drainage group showed a significantly lower trough concentration of VCM (6.2 ± 4.2 µg/mL) than that shown by the nondrainage group (8.5 ± 6.6 µg/mL, p = 0.03). Furthermore, the patients in the drainage group showed a significantly different trough C/D ratio (3.1 ± 2.1) than that shown by the nondrainage group (4.3 ± 3.4, p = 0.014). The Mann-Whitney U test demonstrated significantly lower VCM trough levels with concomitant use of diuretic than without (p = 0.004). Multivariable logistic regression demonstrated that coadministered diuretic independently predicted subtherapeutic trough levels of <10 µg/mL (p = 0.04). The concomitant use of albumin and other variables exerted no effects on VCM trough levels. CONCLUSIONS: These data suggest that CSF drainage and diuretics have different effects, but it seems that both lower the VCM concentration in postoperative neurosurgical patients. Our findings strongly suggest that a high dose of VCM is required to maintain optimal serum concentrations of VCM in patients managed with CSF drainage or concomitant use of diuretic.

Metabolic interactions between flumatinib and the CYP3A4 inhibitors erythromycin, cyclosporine, and voriconazole.

Flumatinib, indicated for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, is a structural analog of imatinib and has shown higher potency than imatinib as a BCR-ABL inhibitor. In this paper, the metabolic profile of flumatinib was studied. It was found that CYP3A4 and CYP2C8 were the main cytochrome P450 enzyme substyles catalyzing the metabolism of flumatinib, and CYP3A4 has a stronger metabolic ability for flumatinib than CYP2C8. Erythromycin, cyclosporine, and voriconazole can inhibit the metabolism of flumatinib in vitro. Accordingly, co-administration of erythromycin and cyclosporine with flumatinib increased the plasma concentration and the systemic exposure of flumatinib in rats, which indicated that lower doses should be considered in clinical practice.

QTc prolongation during antiviral therapy in two COVID-19 patients.

WHAT IS KNOWN AND OBJECTIVE: Acquired long QT syndrome secondary to drug-induced QT prolongation and torsades de pointes has been reported for antiviral drugs. However, no studies have reported an association between corrected QT (QTc) prolongation and antiviral therapy in patients with novel coronavirus disease (COVID-19). CASE DESCRIPTION: We present two cases from our institution in which patients with COVID-19 experienced QTc prolongation during treatment with antiviral therapy. Lopinavir/ritonavir, together with gender and drug-drug interactions, may have contributed to the induction of QTc prolongation in those patients. WHAT IS NEW AND CONCLUSION: Co-administration of QT-prolonging medications and drugs interfering with the metabolism of those medications must be considered in patients with COVID-19. Careful analysis of electrocardiograms for QTc duration should be performed at baseline and during antiviral therapy to identify individuals at high risk of arrhythmias.

Delivery of prazosin hydrochloride from osmotic pump system prepared by coating the core tablet with an indentation.

The preparation of an osmotic pump tablet was simplified by elimination of laser drilling using prazosin hydrochloride as the model drug. The osmotic pump system was obtained by coating the indented core tablet compressed by the punch with a needle. A multiple regression equation was achieved with the experimental data of core tablet formulations, and then the formulation was optimized. The influences of the indentation size of the core tablet, environmental media, and agitation rate on drug release profile were investigated. The optimal osmotic pump tablet was found to deliver prazosin hydrochloride at an approximately constant rate up to 24 hr, and independent on both release media and agitation rate. Indentation size of core tablet hardly affected drug release in the range of 0.80-1.15 mm. The method that is simplified by elimination of laser drilling may be promising for preparation of an osmotic pump tablet.

Preparation and characterization of inclusion complexes of prazosin hydrochloride with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin.

The slightly water-soluble drug prazosin hydrochloride (PRH) and its inclusion with either beta-cyclodextrin (betaCD) or hydroxypropyl-beta-cyclodextrin (HPbetaCD) were investigated. The phase solubility profiles of PRH with betaCD and HPbetaCD were classified as B(s)- and A(L)-types, respectively. Stability constants with 1:1 molar ratio were calculated from the phase solubility diagrams and the solubility of PRH could be enhanced by 27.6% for betaCD and 226.4% for HPbetaCD, respectively. Binary systems of PRH with betaCD or HPbetaCD prepared by various methods were characterized by differential scanning calorimetry and Fourier transformation-infrared spectroscopy. It could be concluded that PRH could form inclusion complex with either betaCD or HPbetaCD. The dissolution profiles of inclusion complexes were determined and compared with those of PRH alone and their physical mixtures. The dissolution rate of PRH was increased by betaCD and HPbetaCD inclusion complexation remarkably. Both the preparation technique and nature of the carriers played important roles in the dissolution performance of the systems. All the systems with HPbetaCD showed better performance than the corresponding ones with betaCD.