Tuning solubility and stability of hydrochlorothiazide co-crystals

Hydrochlorothiazide (HCT), C7H8ClN3O4S2, is a diuretic BCS (Biopharmaceutics Classification System) class IV drug which has primary and secondary sulfonamide groups. To modify the aqueous solubility of the drug, co-crystals with biologically safe co-formers were screened. Multi-component molecular crystals of HCT were prepared with nicotinic acid, nicotinamide, succinamide, p-aminobenzoic acid, resorcinol and pyrogallol using liquid-assisted grinding. The co-crystals were characterized by FT-IR spectroscopy, powder X-ray diffraction (PXRD) and differential scanning calorimetry. Single crystal structures were obtained for four of them. The N-H center dot center dot center dot O sulfonamide catemer synthons found in the stable polymorph of pure HCT are replaced in the co-crystals by drug-co-former heterosynthons. Isostructural co-crystals with nicotinic acid and nicotinamide are devoid of the common sulfonamide dimer/catemer synthons. Solubility and stability experiments were carried out for the co-crystals in water (neutral pH) under ambient conditions. Among the six binary systems, the co-crystal with p-aminobenzoic acid showed a sixfold increase in solubility compared with pure HCT, and stability up to 24 h in an aqueous medium. The co-crystals with nicotinamide, resorcinol and pyrogallol showed only a 1.5-2-fold increase in solubility and transformed to HCT within 1 h of the dissolution experiment. An inverse correlation is observed between the melting points of the co-crystals and their solubilities.

Cocrystals of Hydrochlorothiazide: Solubility and Diffusion/Permeability Enhancements through Drug-Coformer Interactions

Hydrochlorothiazide (HCT) is a diuretic and a BCS class IV drug with low solubility and low permeability, exhibiting poor oral absorption. The present study attempts to improve the physicochemical properties of the drug using a crystal engineering approach with cocrystals. Such multicomponent crystals of HCT with nicotinic acid (NIC), nicotinamide (NCT), 4-aminobenzoic acid (PABA), succinamide (SAM), and resorcinol (RES) were prepared using liquid-assisted grinding, and their solubilities in pH 7.4 buffer were evaluated. Diffusion and membrane permeability were studied using a Franz diffusion cell. Except for the SAM and NIC cocrystals, all other binary systems exhibited improved solubility. All of the cocrystals showed improved diffusion/membrane permeability compared to that of HCT with the exception of the SAM cocrystal. When the solubility was high, as in the case of PABA, NCT, and RES cocrystals, the flux/permeability dropped slightly. This is in agreement with the expected interplay between solubility and permeability. Improved solubility/permeability is attributed to new drug-coformer interactions. Cocrystals of SAM, however, showed poor solubility and flux This cocrystal contains a primary sulfonamide dimer synthon similar to that of HCT polymorphs, which may be a reason for its unusual behavior. Hirshfeld surface analysis was carried out in all cases to determine whether a correlation exists between cocrystal permeability and drug-coformer interactions.

S center dot center dot center dot O chalcogen bonding in sulfa drugs: insights from multipole charge density and X-ray wavefunction of acetazolamide

Experimental charge density analysis combined with the quantum crystallographic technique of X-ray wavefunction refinement (XWR) provides quantitative insights into the intra-and intermolecular interactions formed by acetazolamide, a diuretic drug. Firstly, the analysis of charge density topology at the intermolecular level shows the presence of exceptionally strong interaction motifs such as a DDAA-AADD (D-donor, A-acceptor) type quadruple hydrogen bond motif and a sulfonamide dimer synthon. The nature and strength of intra-molecular S center dot center dot center dot O chalcogen bonding have been characterized using descriptors from the multipole model (MM) and XWR. Although pure geometrical criteria suggest the possibility of two intra-molecular S center dot center dot center dot O chalcogen bonded ring motifs, only one of them satisfies the ``orbital geometry'' so as to exhibit an interaction in terms of an electron density bond path and a bond critical point. The presence of `s-holes' on the sulfur atom leading to the S center dot center dot center dot O chalcogen bond has been visualized on the electrostatic potential surface and Laplacian isosurfaces close to the `reactive surface'. The electron localizability indicator (ELI) and Roby bond orders derived from the `experimental wave function' provide insights into the nature of S center dot center dot center dot O chalcogen bonding.

Acetazolamide polymorphism: a case of hybridization induced polymorphism?

The unusual phenomenon of the formation of the kinetic form as against the thermodynamic form upon slow cooling of boiling aqueous solution in the case of diuretic drug acetazolamide is rationalized in terms of ``hybridization induced polymorphism'' based on extensive experimental and theoretical investigations.

Fatores de risco para ocorrência de restrição do crescimento extra-uterino em prematuros de muito baixo peso ao nascer

A desnutrição em recém-nascidos prematuros de muito baixo peso ao nascer (MBPN) é um fenômeno universal e vem aumentando nas últimas décadas. A restrição do crescimento extra-uterino (RCEU) é um importante indicador do estado nutricional nestes pacientes. O objetivo deste estudo foi identificar os fatores de risco para RCEU durante a internação hospitalar. Foi realizado estudo de coorte retrospectiva que incluiu 188 recém-nascidos MBPN adequados para idade gestacional (AIG), no período de 2002 a 2004. A análise constituiu-se em um modelo de regressão linear longitudinal de efeitos mistos, sendo observada a diferença na taxa de variação do peso para crianças com e sem RCEU na alta hospitalar. Oitenta e sete (46%) dos recém-nascidos incluídos no estudo apresentaram RCEU na alta hospitalar. Influenciaram a taxa de variação do peso ao longo da internação hospitalar: o menor peso ao nascer, sexo masculino, menor Apgar de 5o minuto, o maior escore CRIB; persistência do canal arterial, doença metabólica óssea, hemorragia intracraniana, displasia broncopulmonar e sepse. O maior tempo em oxigenioterapia, as transfusões sanguíneas, o uso de diurético, o maior tempo para atingir dieta plena e de uso de nutrição parenteral também foram preditores do crescimento. A desnutrição de recém-nascidos prematuros MBPN nas Unidades Neonatais é um problema frequente e influenciado tanto pelo cuidado neonatal quanto pelas características individuais de cada criança.

Apneia obstrutiva do sono e função endotelial em pacientes com hipertensão arterial resistente

A apneia obstrutiva do sono (AOS) é considerada um fator de risco independente para as doenças cardiovasculares. Existem evidências de que indivíduos com apneia obstrutiva do sono podem apresentar elevação nos mediadores inflamatórios, alterações no perfil metabólico, aumento na atividade do sistema nervoso simpático, com consequente elevação da pressão arterial e disfunção endotelial. Nos últimos anos, inúmeros estudos tem apontado a AOS como um dos fatores responsáveis pela hipertensão resistente. O objetivo do estudo foi avaliar a presença da apneia obstrutiva do sono e o comportamento da função endotelial em pacientes com hipertensão resistente, comparando com hipertensos apresentando pressão arterial controlada com até 3 classes diferentes de fármacos anti-hipertensivos. Trata-se de um estudo transversal com 40 pacientes hipertensos: 20 com hipertensão arterial resistente (HAR) e 20 com pressão arterial controlada por medicação (hipertensão arterial controlada; HAC), sem distinção de raça ou gênero, com idade entre 18 e 75 anos. A pressão arterial casual e a monitorização ambulatorial da pressão arterial foram aferidas por método oscilométrico em aparelhos automáticos. A função endotelial e a presença da apneia obstrutiva do sono foram avaliadas através da tonometria arterial periférica pelos equipamentos Endo-PAT2000 e o aparelho portátil Watch-PAT200, respectivamente. A avaliação antropométrica foi realizada através das aferições das circunferências da cintura e do pescoço, índice de massa corporal (IMC), e relação cintura-estatura. A composição corporal foi avaliada por bioimpedância elétrica BIODYNAMICS 450. As análises estatísticas foram realizadas pelo software GraphPad PRISM, versão 6.01. A prevalência de AOS no grupo com HAR foi de 85% (Índice de apneia-hipopneia [AHI]= 12,391,89) e de 80% no grupo com HAC (AHI =20,744,69), sendo mais frequente em homens (p=0,04; OR=3,86; 95% IC 0,99 a 14,52). Os dois grupos apresentaram valores semelhantes das variáveis antropométricas avaliadas. A função endotelial avaliada pelo índice de hiperemia reativa foi similar nos dois grupos (grupo HAR: 1,880,09 vs. grupo HAC: 2,030,09; p=0,28). Apesar do número de dessaturações de oxigênio >4% ter apresentado diferença significativa entre os grupos (grupo HAR: 28,755,08 vs. grupo HAC: 64,1516,97; p=0,04), o tempo total de sono (grupo HAR: 309,515,27 vs. grupo HAC: 323,318,74 min) e a saturação mínima da oxi-hemoglobina (grupo HAR: 87,80,85 vs. grupo HAC: 83,32,37%) não mostraram essa diferença. Considerando todos os pacientes hipertensos, o AHI apresentou correlação significativa com o peso corporal (r=0,51; p=0,0007), o IMC (r=0,41; p=0,007), a circunferência da cintura (r=0,44; p=0,005), a circunferência do pescoço (r=0,38; p=0,01) e a relação cintura-estatura (r=0,39; p=0,01). Os pacientes sem AOS em comparação com os pacientes com AOS, apresentaram risco significativamente menor de apresentar comprometimento da função endotelial (OR=0,17; 95% IC 0,04-0,72; p=0,03). Os achados do presente estudo sugerem que a prevalência de AOS em pacientes com hipertensão resistente é elevada, porém semelhante a de indivíduos com hipertensão controlada. Pacientes com hipertensão resistente e controlada não apresentaram diferenças significativas em relação à função endotelial. A gravidade de AOS no grupo total de hipertensos se associou com maior risco de comprometimento da função endotelial.

Avaliação da função endotelial em pacientes com hipertensão arterial resistente

A hipertensão arterial resistente (HAR) é definida pela persistência da pressão arterial (PA)≥140/90mmHg a despeito do uso de 3 anti-hipertensivos em doses plenas, incluindo diurético. Revisão recente da literatura mostra poucos estudos avaliando o perfil e o comportamento da função endotelial em pacientes com HAR. Objetiva avaliar a função endotelial em pacientes hipertensos resistentes. Estudo transversal com 60 pacientes que foram avaliados em uma visita (V3) de um estudo longitudinal, onde numa primeira fase todos pacientes tiveram padronização do tratamento anti-hipertensivo. Foram incluídos pacientes (V0) com PA>160/100mmHg e <220mmHg e todos receberam clortalidona 25mg/dia e enalapril 20mg 2x/dia ou losartana 50mg 2x/dia (intolerantes ao enalapril). Visita 1: se PA>140/90mmHg acrescentou-se anlodipino 5mg/dia, foi realizado avaliação laboratorial de rotina do hipertenso e monitorização ambulatorial da PA-24h (MAPA). Visita 2: se PA>140/90mmHganlodipino foi titulado para 10mg/dia. Visita 3: todos os pacientes receberam avaliação clínica, da pressão arterial por MAPA, laboratorial de rotina e da função endotelial. Formaram-se dois grupos: os que controlaram a PA, grupo hipertensão arterial controlada (HAC); e os que permaneceram com PA de consultório>140/90mmHg e PA na MAPA-24h>130/80mmHg, foram considerados resistentes. O grupo HAR recebeu aleatoriamente espironolactona ou clonidina por mais 12 semanas para tentar controlar a PA e o grupo HAC teve assistência farmacológica mantida no mesmo período. A PA foi avaliada por método oscilométrico com aparelho digital semi-automático Microlife modelo BP3AC1-1PC e MAPA por aparelho SpaceLabs 90207. A função endotelial avaliada através de tonometria arteriolar periférica (PAT) pelo Endo-PAT2000 e por biomarcadores (I-CAM-1, V-CAM-1, VEGF, MCP-1, IL-6, adiponectina) através da técnica LuminexTMxMAP. Dos 60 pacientes avaliados, 36 controlaram a PA, grupo HAC, e 24 permaneceram resistentes ao tratamento, grupo HAR, na visitaV3. Na avaliação da PA pela MAPA-24h observamos que no grupo HAC a PAS-24h foi de 121,1+1,7mmHg e no grupo HAR 147+3,3mmHg, enquanto a PAD-24h no grupo HAC foi de 76,64+1,5mmHg e no grupo HAR 88,58+2,4mmHg (p<0,0001). O descenso noturno, apesar de maior no grupo HAC, não apresentou significância estatística entre os dois grupos (p> 0,05). A função endotelial avaliada através do PAT mostrou índice de hiperemia reativa de 1,850,056 e 1,65+0,074 nos grupos HAC e HAR respectivamente (p= 0,036) e quando avaliada através dos biomarcadores observamos: ICAM-1 (HAC= 186,6+12,65 vs HAR= 240,9+23,76ng/ml, p= 0,038), VCAM-1 (HAC= 627,137,09vs HAR= 706,086,10ng/ml, p= 0,372),VEGF (HAC= 403,394,91 vs HAR= 612,788,27pg/ml, p= 0,123) e MCP-1 (HAC= 694,969,09 vs HAR= 787,052,80pg/ml, p= 0,315). Na avaliação dos biomarcadores inflamatórios, observamos IL-6 no grupo HAC= 1,8970,2165pg/mle no HAR= 9,7934,421pg/ml (p= 0,027) e adiponectina no grupo HAC= 105701516pg/ml e HAR= 84221295pg/ml (p=0,301). A razão de prevalência do comprometimento da função endotelial no grupo HAR foi de 54% (OR= 3,55; 95% IC 1,18- 10.67; p= 0,029). No presente trabalho, as análises das variáveis estudadas na visita V3, mostraram que os pacientes com HAR têm maior comprometimento da função endotelial que os pacientes com HAC.

A Fitoterapia no tratamento da obesidade

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Apparent treatment-resistant hypertension and chronic kidney disease: another cardiovascular-renal syndrome?

To identify patients at increased risk of cardiovascular (CV) outcomes, apparent treatment-resistant hypertension (aTRH) is defined as having a blood pressure above goal despite the use of 3 or more antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. Recent epidemiologic studies in selected populations estimated the prevalence of aTRH as 10% to 15% among patients with hypertension and that aTRH is associated with elevated risk of CV and renal outcomes. Additionally, aTRH and CKD are associated. Although the pathogenesis of aTRH is multifactorial, the kidney is believed to play a significant role. Increased volume expansion, aldosterone concentration, mineralocorticoid receptor activity, arterial stiffness, and sympathetic nervous system activity are central to the pathogenesis of aTRH and are targets of therapies. Although diuretics form the basis of therapy in aTRH, pathophysiologic and clinical data suggest an important role for aldosterone antagonism. Interventional techniques, such as renal denervation and carotid baroreceptor activation, modulate the sympathetic nervous system and are currently in phase III trials for the treatment of aTRH. These technologies are as yet unproven and have not been investigated in relationship to CV outcomes or in patients with CKD.

Phenolic compounds, antioxidant and antibacterial activities of three Ericaceae from Algeria

Herbs of the Ericaceae family are commonly found in Algeria and used in traditional medicine as anti- septic, diuretic, astringent, depurative, and to treat scalds and wounds. The methanolic extracts of three species, Arbutus unedo L. (A. unedo, leaves), Erica arborea L. (E. arborea, flowered aerial parts), and Erica multiflora L. (E. multiflora, flowered aerial parts), were compared regarding their content in pheno- lic compounds, their antioxidant, and antibacterial activities. A. unedo harbors the highest content in total phenolics and flavonoids, followed by E. arborea E. multiflora. The contents in total phenolics and flavonoids showed a correlation with the measured antioxidant (hydrogen-donating) activities; this was particularly the case for flavonoids content. The A. unedo extract showed antibacterial activity against all the tested strains (Staphylococcus aureus ATCC 6538, S. aureus C100459, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 9027); however, the E. arborea and E. multiflora extracts showed antibacterial activity only against Gram positive bacteria. Some polyphenols were identified in the three herbs by thin-layer chromatography and high-performance liquid chromatography coupled with diode array and mass spectrometry detection; from these, caffeic acid, p-coumaric acid, naringin, quercetin and kaempferol are reported for the first time in E. multiflora.

The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease

BACKGROUND: Hypertension and cognitive impairment are prevalent in older people. It is known that hypertension is a direct risk factor for vascular dementia and recent studies have suggested hypertension also impacts upon prevalence of Alzheimer's disease. The question is therefore whether treatment of hypertension lowers the rate of cognitive decline. OBJECTIVES: To assess the effects of blood pressure lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease. SEARCH STRATEGY: The trials were identified through a search of CDCIG's Specialised Register, CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL on 27 April 2005. SELECTION CRITERIA: Randomized, double-blind, placebo controlled trials in which pharmacological or non-pharmacological interventions to lower blood pressure were given for at least six months. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and extracted data. The following outcomes were assessed: incidence of dementia, cognitive change from baseline, blood pressure level, incidence and severity of side effects and quality of life. MAIN RESULTS: Three trials including 12,091 hypertensive subjects were identified. Average age was 72.8 years. Participants were recruited from industrialised countries. Mean blood pressure at entry across the studies was 170/84 mmHg. All trials instituted a stepped care approach to hypertension treatment, starting with a calcium-channel blocker, a diuretic or an angiotensin receptor blocker. The combined result of the three trials reporting incidence of dementia indicated no significant difference between treatment and placebo (Odds Ratio (OR) = 0.89, 95% CI 0.69, 1.16). Blood pressure reduction resulted in a 11% relative risk reduction of dementia in patients with no prior cerebrovascular disease but this effect was not statistically significant (p = 0.38) and there was considerable heterogeneity between the trials. The combined results from the two trials reporting change in Mini Mental State Examination (MMSE) did not indicate a benefit from treatment (Weighted Mean Difference (WMD) = 0.10, 95% CI -0.03, 0.23). Both systolic and diastolic blood pressure levels were reduced significantly in the two trials assessing this outcome (WMD = -7.53, 95% CI -8.28, -6.77 for systolic blood pressure, WMD = -3.87, 95% CI -4.25, -3.50 for diastolic blood pressure).Two trials reported adverse effects requiring discontinuation of treatment and the combined results indicated a significant benefit from placebo (OR = 1.18, 95% CI 1.06, 1.30). When analysed separately, however, more patients on placebo in SCOPE were likely to discontinue treatment due to side effects; the converse was true in SHEP 1991. Quality of life data could not be analysed in the three studies. There was difficulty with the control group in this review as many of the control subjects received antihypertensive treatment because their blood pressures exceeded pre-set values. In most cases the study became a comparison between the study drug against a usual antihypertensive regimen. AUTHORS' CONCLUSIONS: There was no convincing evidence from the trials identified that blood pressure lowering prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease. There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients given active treatment. This introduced bias. More robust results may be obtained by analysing one year data to reduce differential drop-out or by conducting a meta-analysis using individual patient data.

TAZ Expression as a Prognostic Indicator in Colorectal Cancer

The Hippo pathway restricts the activity of transcriptional coactivators TAZ (WWTR1) and YAP. TAZ and YAP are reported to be overexpressed in various cancers, however, their prognostic significance in colorectal cancers remains unstudied. The expression levels of TAZ and YAP, and their downstream transcriptional targets, AXL and CTGF, were extracted from two independent colon cancer patient datasets available in the Gene Expression Omnibus database, totaling 522 patients. We found that mRNA expressions of both TAZ and YAP were positively correlated with those of AXL and CTGF (p<0.05). High level mRNA expression of TAZ, AXL or CTGF significantly correlated with shorter survival. Importantly, patients co-overexpressing all 3 genes had a significantly shorter survival time, and combinatorial expression of these 3 genes was an independent predictor for survival. The downstream target genes for TAZ-AXL-CTGF overexpression were identified by Java application MyStats. Interestingly, genes that are associated with colon cancer progression (ANTXR1, EFEMP2, SULF1, TAGLN, VCAN, ZEB1 and ZEB2) were upregulated in patients co-overexpressing TAZ-AXL-CTGF. This TAZ-AXL-CTGF gene expression signature (GES) was then applied to Connectivity Map to identify small molecules that could potentially be utilized to reverse this GES. Of the top 20 small molecules identified by connectivity map, amiloride (a potassium sparing diuretic,) and tretinoin (all-trans retinoic acid) have shown therapeutic promise in inhibition of colon cancer cell growth. Using MyStats, we found that low level expression of either ANO1 or SQLE were associated with a better prognosis in patients who co-overexpressed TAZ-AXL-CTGF, and that ANO1 was an independent predictor of survival together with TAZ-AXL-CTGF. Finally, we confirmed that TAZ regulates Axl, and plays an important role in clonogenicity and non-adherent growth in vitro and tumor formation in vivo. These data suggest that TAZ could be a therapeutic target for the treatment of colon cancer.

Enhanced clinical pharmacy service targeting tools: risk-predictive algorithms

Rationale, aims and objectives: This study aimed to determine the value of using a mix of clinical pharmacy data and routine hospital admission spell data in the development of predictive algorithms. Exploration of risk factors in hospitalized patients, together with the targeting strategies devised, will enable the prioritization of clinical pharmacy services to optimize patient outcomes. 

Methods: Predictive algorithms were developed using a number of detailed steps using a 75% sample of integrated medicines management (IMM) patients, and validated using the remaining 25%. IMM patients receive targeted clinical pharmacy input throughout their hospital stay. The algorithms were applied to the validation sample, and predicted risk probability was generated for each patient from the coefficients. Risk threshold for the algorithms were determined by identifying the cut-off points of risk scores at which the algorithm would have the highest discriminative performance. Clinical pharmacy staffing levels were obtained from the pharmacy department staffing database. 

Results: Numbers of previous emergency admissions and admission medicines together with age-adjusted co-morbidity and diuretic receipt formed a 12-month post-discharge and/or readmission risk algorithm. Age-adjusted co-morbidity proved to be the best index to predict mortality. Increased numbers of clinical pharmacy staff at ward level was correlated with a reduction in risk-adjusted mortality index (RAMI). 

Conclusions: Algorithms created were valid in predicting risk of in-hospital and post-discharge mortality and risk of hospital readmission 3, 6 and 12 months post-discharge. The provision of ward-based clinical pharmacy services is a key component to reducing RAMI and enabling the full benefits of pharmacy input to patient care to be realized.

Logic Programming and Artificial Neural Networks in Pharmacological Screening of Schinus Essential Oils

Some plants of genus Schinus have been used in the folk medicine as topical antiseptic, digestive, purgative, diuretic, analgesic or antidepressant, and also for respiratory and urinary infections. Chemical composition of essential oils of S. molle and S. terebinthifolius had been evaluated and presented high variability according with the part of the plant studied and with the geographic and climatic regions. The pharmacological properties, namely antimicrobial, anti-tumoural and anti-inflammatory activities are conditioned by chemical composition of essential oils. Taking into account the difficulty to infer the pharmacological properties of Schinus essential oils without hard experimental approach, this work will focus on the development of a decision support system, in terms of its knowledge representation and reasoning procedures, under a formal framework based on Logic Programming, complemented with an approach to computing centered on Artificial Neural Networks and the respective Degree-of-Confidence that one has on such an occurrence.

A randomized trial to assess the potential of different beverages to affect hydration status: development of a beverage hydration index

Background: The identification of beverages that promote longer- term fluid retention and maintenance of fluid balance is of real clinical and practical benefit in situations in which free access to fluids is limited or when frequent breaks for urination are not desirable. The postingestion diuretic response is likely to be influenced by several beverage characteristics, including the volume ingested, energy den- sity, electrolyte content, and the presence of diuretic agents. Objective: This study investigated the effects of 13 different com- monly consumed drinks on urine output and fluid balance when ingested in a euhydrated state, with a view to establishing a beverage hydration index (BHI), i.e., the volume of urine produced after drinking expressed relative to a standard treatment (still water) for each beverage. Design: Each subject (n = 72, euhydrated and fasted male subjects) ingested 1 L still water or 1 of 3 other commercially available beverages over a period of 30 min. Urine output was then collected for the subsequent 4 h. The BHI was corrected for the water content of drinks and was calculated as the amount of water retained at 2 h after ingestion relative to that observed after the ingestion of still water. Results: Total urine masses (mean 6 SD) over 4 h were smaller than the still-water control (1337 6 330 g) after an oral rehydration solution (ORS) (1038 6 333 g, P , 0.001), full-fat milk (1052 6 267 g, P , 0.001), and skimmed milk (1049 6 334 g, P , 0.001). Cumulative urine output at 4 h after ingestion of cola, diet cola, hot tea, iced tea, coffee, lager, orange juice, sparkling water, and a sports drink were not different from the response to water ingestion. The mean BHI at 2 h was 1.54 6 0.74 for the ORS, 1.50 6 0.58 for full- fat milk, and 1.58 6 0.60 for skimmed milk. Conclusions: BHI may be a useful measure to identify the short- term hydration potential of different beverages when ingested in a euhydrated state.