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Khashayar Sakhaee - One of the best experts on this subject based on the ideXlab platform.
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fasting versus 24 h Urine pH in the evaluation of nepHrolithiasis
Urological Research, 2011Co-Authors: Giovanna Capolongo, Khashayar Sakhaee, Naim M MaaloufAbstract:An abnormal urinary pH (UpH) represents an important risk factor for nepHrolithiasis. In some stone formers, a fasting Urine specimen is obtained instead of a 24-h Urine collection for stone risk evaluation. We examined the relationship between 24-h and fasting UpH in non-stone forming individuals and stone formers with various etiologies and a wide range of Urine pH to test the validity of fasting UpH. Data from 159 subjects was examined in this retrospective study. We included non-stone forming subjects and stone formers with hypercalciuria, distal renal tubular acidosis, idiopathic uric acid nepHrolithiasis, or chronic diarrhea. Participants collected a 24-h Urine followed by a 2-h fasting Urine. For the entire cohort, a significant correlation was seen between fasting and 24-h UpH (r2 = 0.49, p 0.2 pH units different from 24-h UpH in 58% of participants. The difference between fasting and 24-h UpH did not correlate with net gastrointestinal alkali absorption or Urine sulfate, suggesting that dietary factors alone cannot explain this difference in UpH. Fasting Urine pH correlates moderately with 24-h Urine pH in a large cohort of individuals. Significant variability between these two parameters is seen in individual patients, empHasizing the cardinal role of 24-h Urine collection for evaluating UpH in nepHrolithiasis.
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metabolic basis for low Urine pH in type 2 diabetes
Clinical Journal of The American Society of Nephrology, 2010Co-Authors: Naim M Maalouf, Mary Ann Cameron, Khashayar SakhaeeAbstract:Background and objectives: Type 2 diabetes is associated with excessively low Urine pH, which increases the risk for uric acid nepHrolithiasis. This study was conducted to assess the metabolic basis responsible for the excessive urinary acidity of individuals with type 2 diabetes. Design, setting, participants, & measurements: Nine non–stone-forming patients who had type 2 diabetes and low Urine pH and 16 age- and body mass index–matched non–stone-forming volunteers without type 2 diabetes were maintained on a constant metabolic diet for 7 days, and 24-hour Urine was collected on the last 2 days of the diet. Results: Urine dietary markers (potassium, sulfate, pHospHorus, and urea nitrogen) were not different between the two groups. Patients with type 2 diabetes exhibited a significantly lower 24-hour Urine pH (5.45 ± 0.27 versus 5.90 ± 0.42; P < 0.01) and higher net acid excretion (NAE; 57 ± 12 versus 38 ± 18 mEq/d; P < 0.01) compared with control subjects. The proportion of NAE excreted as ammonium (NH4+/NAE) was significantly lower in patients with type 2 diabetes than in control subjects (0.70 ± 0.12 versus 0.94 ± 0.36; P < 0.01); however, the greater NAE in patients with type 2 diabetes was not accounted for by the differences in unmeasured urinary anions. Conclusions: The overly acidic Urine in patients with type 2 diabetes persists after controlling for dietary factors, body size, and age. The lower pH is due to a combination of greater NAE and lower use of ammonia buffers in patients with diabetes, which predisposes them to uric acid urolithiasis.
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Metabolic basis for low Urine pH in type 2 diabetes
Clinical Journal of the American Society of Nephrology, 2010Co-Authors: Naim M Maalouf, Mary Ann Cameron, Orson W. Moe, Khashayar SakhaeeAbstract:Type 2 diabetes is associated with excessively low Urine pH, which increases the risk for uric acid nepHrolithiasis. This study was conducted to assess the metabolic basis responsible for the excessive urinary acidity of individuals with type 2 diabetes.
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low Urine pH a novel feature of the metabolic syndrome
Clinical Journal of The American Society of Nephrology, 2007Co-Authors: Naim M Maalouf, Mary Ann Cameron, Beverley Adamshuet, Khashayar SakhaeeAbstract:Background and Objectives: The metabolic syndrome is associated with alterations in renal function. An overly acidic Urine has been described as a renal manifestation of the metabolic syndrome in patients with kidney stone disease. This study examined the association between the metabolic syndrome and Urine pH in individuals without a history of nepHrolithiasis. Design, Setting, Participants, & Measurements: A total of 148 adults who were free of kidney stones were evaluated in this outpatient cross-sectional study. Height, weight, BP, fasting blood, and 24-h Urine chemistries were obtained. Urine pH was measured by pH electrode. The following features of the metabolic syndrome were evaluated: BP; body mass index; and serum triglyceride, glucose, and HDL cholesterol concentrations. The degree of insulin resistance was assessed by the homeostasis model assessment of insulin resistance. Results: Participants with the metabolic syndrome had a significantly lower 24-h Urine pH compared with participants without the metabolic syndrome. Mean 24-h Urine pH, adjusted for age, gender, creatinine clearance, and 24-h Urine sulfate, decreased from 6.15, 6.10, 5.99, 5.85, to 5.69 with increasing number of metabolic syndrome abnormalities. An association was observed between 24-h Urine pH and each metabolic feature. After adjustment for age, gender, creatinine clearance, Urine sulfate, and body mass index, a significant inverse relationship was noted between 24-h Urine pH and the degree of insulin resistance. Conclusions: An unduly acidic Urine is a feature of the metabolic syndrome and is associated with the degree of insulin resistance.
Naim M Maalouf - One of the best experts on this subject based on the ideXlab platform.
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Effect of Urine pH and magnesium on calcium oxalate saturation.
Magnesium Research, 2017Co-Authors: Silvia Ferre, Jacob S Grange, Beverley Adamshuet Ms, Naim M MaaloufAbstract:: Hypomagnesiuria is a common biochemical finding in patients with calcium oxalate (CaOx) nepHrolithiasis. Clinical trials using Mg supplements as therapy against CaOx stones have shown mixed results. We tested the effect of Mg administration in healthy subjects under conditions of controlled Urine pH (UpH) on urinary Ca excretion rate (UCaV) and CaOx saturation. This is a 4-pHase, double blind, placebo-controlled, metabolic crossover study performed in healthy volunteers. Mg lactate (MgLact2) was used as Mg supplement. High UpH and low UpH were achieved by administration of potassium citrate (K3Citrate) and ammonium chloride (NH4Cl), respectively, with potassium balance maintained by KCl. Eight participants completed 4 pHases of study. The interventions successfully modulated 24-h UpH (7.0 ± 0.4 vs. 5.7 ± 0.6 in high vs low pH pHases; P
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effect of Urine pH and magnesium on calcium oxalate saturation
Magnesium Research, 2017Co-Authors: Silvia Ferre, Jacob S Grange, Beverley Adamshuet Ms, Naim M MaaloufAbstract:: Hypomagnesiuria is a common biochemical finding in patients with calcium oxalate (CaOx) nepHrolithiasis. Clinical trials using Mg supplements as therapy against CaOx stones have shown mixed results. We tested the effect of Mg administration in healthy subjects under conditions of controlled Urine pH (UpH) on urinary Ca excretion rate (UCaV) and CaOx saturation. This is a 4-pHase, double blind, placebo-controlled, metabolic crossover study performed in healthy volunteers. Mg lactate (MgLact2) was used as Mg supplement. High UpH and low UpH were achieved by administration of potassium citrate (K3Citrate) and ammonium chloride (NH4Cl), respectively, with potassium balance maintained by KCl. Eight participants completed 4 pHases of study. The interventions successfully modulated 24-h UpH (7.0 ± 0.4 vs. 5.7 ± 0.6 in high vs low pH pHases; P<0.001). Administration of MgLact2 increased UMgV [175.8 ± 40.2 vs 93.4 ± 39.7 mg/day (7.2 ± 1.7 vs 3.8 ± 1.6 mmol/day), high vs low Mg pHase; P<0.001], and increased pH both at low (5.6 ± 0.5 to 5.8 ± 0.7; P = 0.02) and high UpH (6.9 ± 0.4 to 7.0 ± 0.3; P = 0.01). At a given Urine pH, Mg supplementation marginally increased UCaV, but did not alter UOxV or CaOx saturation. Provision of an alkali load significantly lowered UCaV and saturation of CaOx at any level of UMgV. Compared to changes in UMgV, changes in UpH play a more significant role in determining Urine CaOx saturation in healthy subjects. Mg supplements are likely to reduce CaOx saturation if they also raise Urine pH.
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fasting versus 24 h Urine pH in the evaluation of nepHrolithiasis
Urological Research, 2011Co-Authors: Giovanna Capolongo, Khashayar Sakhaee, Naim M MaaloufAbstract:An abnormal urinary pH (UpH) represents an important risk factor for nepHrolithiasis. In some stone formers, a fasting Urine specimen is obtained instead of a 24-h Urine collection for stone risk evaluation. We examined the relationship between 24-h and fasting UpH in non-stone forming individuals and stone formers with various etiologies and a wide range of Urine pH to test the validity of fasting UpH. Data from 159 subjects was examined in this retrospective study. We included non-stone forming subjects and stone formers with hypercalciuria, distal renal tubular acidosis, idiopathic uric acid nepHrolithiasis, or chronic diarrhea. Participants collected a 24-h Urine followed by a 2-h fasting Urine. For the entire cohort, a significant correlation was seen between fasting and 24-h UpH (r2 = 0.49, p 0.2 pH units different from 24-h UpH in 58% of participants. The difference between fasting and 24-h UpH did not correlate with net gastrointestinal alkali absorption or Urine sulfate, suggesting that dietary factors alone cannot explain this difference in UpH. Fasting Urine pH correlates moderately with 24-h Urine pH in a large cohort of individuals. Significant variability between these two parameters is seen in individual patients, empHasizing the cardinal role of 24-h Urine collection for evaluating UpH in nepHrolithiasis.
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metabolic basis for low Urine pH in type 2 diabetes
Clinical Journal of The American Society of Nephrology, 2010Co-Authors: Naim M Maalouf, Mary Ann Cameron, Khashayar SakhaeeAbstract:Background and objectives: Type 2 diabetes is associated with excessively low Urine pH, which increases the risk for uric acid nepHrolithiasis. This study was conducted to assess the metabolic basis responsible for the excessive urinary acidity of individuals with type 2 diabetes. Design, setting, participants, & measurements: Nine non–stone-forming patients who had type 2 diabetes and low Urine pH and 16 age- and body mass index–matched non–stone-forming volunteers without type 2 diabetes were maintained on a constant metabolic diet for 7 days, and 24-hour Urine was collected on the last 2 days of the diet. Results: Urine dietary markers (potassium, sulfate, pHospHorus, and urea nitrogen) were not different between the two groups. Patients with type 2 diabetes exhibited a significantly lower 24-hour Urine pH (5.45 ± 0.27 versus 5.90 ± 0.42; P < 0.01) and higher net acid excretion (NAE; 57 ± 12 versus 38 ± 18 mEq/d; P < 0.01) compared with control subjects. The proportion of NAE excreted as ammonium (NH4+/NAE) was significantly lower in patients with type 2 diabetes than in control subjects (0.70 ± 0.12 versus 0.94 ± 0.36; P < 0.01); however, the greater NAE in patients with type 2 diabetes was not accounted for by the differences in unmeasured urinary anions. Conclusions: The overly acidic Urine in patients with type 2 diabetes persists after controlling for dietary factors, body size, and age. The lower pH is due to a combination of greater NAE and lower use of ammonia buffers in patients with diabetes, which predisposes them to uric acid urolithiasis.
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Metabolic basis for low Urine pH in type 2 diabetes
Clinical Journal of the American Society of Nephrology, 2010Co-Authors: Naim M Maalouf, Mary Ann Cameron, Orson W. Moe, Khashayar SakhaeeAbstract:Type 2 diabetes is associated with excessively low Urine pH, which increases the risk for uric acid nepHrolithiasis. This study was conducted to assess the metabolic basis responsible for the excessive urinary acidity of individuals with type 2 diabetes.
Mitchell L. Halperin - One of the best experts on this subject based on the ideXlab platform.
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Studies to identify the basis for an alkaline Urine pH in patients with calcium hydrogen pHospHate kidney stones
Nephrology Dialysis Transplantation, 2006Co-Authors: Kamel S. Kamel, Mohammad A. Shafiee, Surinder Cheema-dhadli, Mitchell L. HalperinAbstract:BACKGROUND: Patients with CaHPO(4) kidney stones belong to a diagnostic category that has a high Urine pH as its common feature. Our objective was to provide a new clinical approach to examine the basis for this high pH. METHODS: The study group consisted of 26 CaHPO(4) stone formers and 28 normal volunteers. Urine was collected q2h plus an overnight sample to identify patients with a Urine pH > 6.5 for 12/24 h. Urine ammonium (U(NH4)), sulpHate (U(SO4)) and citrate were measured and diet net alkali was calculated. RESULTS: Of the 26 patients, 13 had persistently alkaline Urine. In 7/13, U(NH4) (68 +/- 13 mEq/day) and U(SO4) (57 +/- 7 mEq/day) were both high. In 6/13 patients, U(NH4) was the usual 31 +/- 3 mEq/day; in 4/6, U(NH4)/U(SO4) was 0.9 +/- 0.1; the cause of the alkaline Urine pH seemed to be a dietary alkali load because the rise in Urine pH was episodic and coincided with a high net diet alkali load and peak citrate excretion rates. The remaining two patients had a high U(NH4)/U(SO4) (2.2 and 1.6). Citrate excretion was very low in the male, but not in the female patient. CONCLUSIONS: There are heterogeneous causes for a persistently high Urine pH. Two of the patients had a possible molecular basis: the lesion could be a low proximal convoluted tubule cell pH in the male and an increased entry of NH(3) into the late distal nepHron in the female.
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studies on the pathopHysiology of the low Urine pH in patients with uric acid stones
Kidney International, 2002Co-Authors: Kamel S. Kamel, Surinder Cheemadhadli, Mitchell L. HalperinAbstract:Studies on the pathopHysiology of the low Urine pH in patients with uric acid stones. Background A very low Urine pH is the major risk factor for uric acid stone formation. Methods A subgroup of patients with a history of uric acid stones and a persistently low Urine pH ( 4 + ) and sulfate (SO 4 2- ) excretions, patients were divided into two groups. Results The first group ( N = 2) excreted 173 and 139% more NH 4 + than SO 4 2- . Their daily urinary unmeasured anion excretion was higher than their calculated net diet alkali input (38 and 61 vs. 24 and 49 mEq, respectively). In the second group ( N = 12), NH 4 + excretion was 69 ± 5% that of SO 4 2- . In 2 of 12, decreased renal ammoniagenesis was suspected due to a plasma potassium of 5.3mmol/L and/or a lower GFR (65 and 59 L/day); these patients had an extremely low citrate excretion (3 and 1 mEq/day). In contrast, citrate excretion was not low in the remaining 10 patients (10.4 ± 1.3 mEq/day). Conclusions Patients in group 1 needed a higher NH 4 + excretion possibly because of a H + load from excessive renal excretion of organic anions. We speculate that an alkaline proximal tubular cell pH could be the basis for the low NH 4 + and high citrate excretions in 10 of 12 patients in group 2. Dietary factors and/or a molecular lesion may contribute to their pathopHysiology.
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renal tubular acidosis rta recognize the ammonium defect and pHorget the Urine pH
Pediatric Nephrology, 1991Co-Authors: Euan Carlisle, Sandra Donnelly, Mitchell L. HalperinAbstract:To maintain acid-base balance, the kidney must generate new bicarbonate by metabolizing glutamine and excreting ammonium (NH4 +). During chronic metabolic acidosis, the kidney should respond by increasing the rate of excretion of NH4 + to 200–300 mmol/day. If the rate of excretion of NH4 + is much lower, the kidney is responsible for causing or perpetuating the chronic metabolic acidosis. Thus, the first step in the assessment of hyperchloraemic metabolic acidosis is to evaluate the rate of excretion of NH4 +. It is important to recognize that the Urine pH may be misleading when initially assessing the cause of this acidosis, as it does not necessarily reflect the rate of excretion of NH4 +. If proximal renal tubular acidosis (RTA) is excluded, low NH4 + excretion disease may be broadly classified into problems of NH4 + production and problems of NH4 + transfer to the Urine; the latter being due to either interstitial disease or disorders of hydrogen ion secretion. The measurement of the Urine pH at this stage may identify which problem predominates. This approach returns the focus of the investigation of RTA from Urine pH to Urine NH4 +.
Mary Ann Cameron - One of the best experts on this subject based on the ideXlab platform.
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metabolic basis for low Urine pH in type 2 diabetes
Clinical Journal of The American Society of Nephrology, 2010Co-Authors: Naim M Maalouf, Mary Ann Cameron, Khashayar SakhaeeAbstract:Background and objectives: Type 2 diabetes is associated with excessively low Urine pH, which increases the risk for uric acid nepHrolithiasis. This study was conducted to assess the metabolic basis responsible for the excessive urinary acidity of individuals with type 2 diabetes. Design, setting, participants, & measurements: Nine non–stone-forming patients who had type 2 diabetes and low Urine pH and 16 age- and body mass index–matched non–stone-forming volunteers without type 2 diabetes were maintained on a constant metabolic diet for 7 days, and 24-hour Urine was collected on the last 2 days of the diet. Results: Urine dietary markers (potassium, sulfate, pHospHorus, and urea nitrogen) were not different between the two groups. Patients with type 2 diabetes exhibited a significantly lower 24-hour Urine pH (5.45 ± 0.27 versus 5.90 ± 0.42; P < 0.01) and higher net acid excretion (NAE; 57 ± 12 versus 38 ± 18 mEq/d; P < 0.01) compared with control subjects. The proportion of NAE excreted as ammonium (NH4+/NAE) was significantly lower in patients with type 2 diabetes than in control subjects (0.70 ± 0.12 versus 0.94 ± 0.36; P < 0.01); however, the greater NAE in patients with type 2 diabetes was not accounted for by the differences in unmeasured urinary anions. Conclusions: The overly acidic Urine in patients with type 2 diabetes persists after controlling for dietary factors, body size, and age. The lower pH is due to a combination of greater NAE and lower use of ammonia buffers in patients with diabetes, which predisposes them to uric acid urolithiasis.
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Metabolic basis for low Urine pH in type 2 diabetes
Clinical Journal of the American Society of Nephrology, 2010Co-Authors: Naim M Maalouf, Mary Ann Cameron, Orson W. Moe, Khashayar SakhaeeAbstract:Type 2 diabetes is associated with excessively low Urine pH, which increases the risk for uric acid nepHrolithiasis. This study was conducted to assess the metabolic basis responsible for the excessive urinary acidity of individuals with type 2 diabetes.
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low Urine pH a novel feature of the metabolic syndrome
Clinical Journal of The American Society of Nephrology, 2007Co-Authors: Naim M Maalouf, Mary Ann Cameron, Beverley Adamshuet, Khashayar SakhaeeAbstract:Background and Objectives: The metabolic syndrome is associated with alterations in renal function. An overly acidic Urine has been described as a renal manifestation of the metabolic syndrome in patients with kidney stone disease. This study examined the association between the metabolic syndrome and Urine pH in individuals without a history of nepHrolithiasis. Design, Setting, Participants, & Measurements: A total of 148 adults who were free of kidney stones were evaluated in this outpatient cross-sectional study. Height, weight, BP, fasting blood, and 24-h Urine chemistries were obtained. Urine pH was measured by pH electrode. The following features of the metabolic syndrome were evaluated: BP; body mass index; and serum triglyceride, glucose, and HDL cholesterol concentrations. The degree of insulin resistance was assessed by the homeostasis model assessment of insulin resistance. Results: Participants with the metabolic syndrome had a significantly lower 24-h Urine pH compared with participants without the metabolic syndrome. Mean 24-h Urine pH, adjusted for age, gender, creatinine clearance, and 24-h Urine sulfate, decreased from 6.15, 6.10, 5.99, 5.85, to 5.69 with increasing number of metabolic syndrome abnormalities. An association was observed between 24-h Urine pH and each metabolic feature. After adjustment for age, gender, creatinine clearance, Urine sulfate, and body mass index, a significant inverse relationship was noted between 24-h Urine pH and the degree of insulin resistance. Conclusions: An unduly acidic Urine is a feature of the metabolic syndrome and is associated with the degree of insulin resistance.
Amin Rostamihodjegan - One of the best experts on this subject based on the ideXlab platform.
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towards further verification of pHysiologically based kidney models predictability of the effects of Urine flow and Urine pH on renal clearance
Journal of Pharmacology and Experimental Therapeutics, 2019Co-Authors: Takanobu Matsuzaki, Daniel Scotcher, Adam S Darwich, Aleksandra Galetin, Amin RostamihodjeganAbstract:In vitro-in vivo extrapolation (IVIVE) of renal excretory clearance (CLR) using the pHysiologically based kidney models can provide mechanistic insight into the interplay of multiple processes occurring in the renal tubule; however, the ability of these models to capture quantitatively the impact of perturbed conditions (e.g., Urine flow, Urine pH changes) on CLR has not been fully evaluated. In this work, we aimed to assess the predictability of the effect of Urine flow and Urine pH on CLR and tubular drug concentrations (selected examples). Passive diffusion clearance across the nepHron tubule membrane was scaled from in vitro human epithelial cell line Caco-2 permeability data by nepHron tubular surface area to predict the fraction reabsorbed and the CLR of caffeine, chlorampHenicol, creatinine, dextroampHetamine, nicotine, sulfamethoxazole, and theopHylline. CLR values predicted using mechanistic kidney model at a urinary pH of 6.2 and 7.4 resulted in prediction bias of 2.87- and 3.62-fold, respectively. Model simulations captured Urine flow–dependent CLR, albeit with minor underprediction of the observed magnitude of change. The relationship between drug solubility, Urine flow, and Urine pH, illustrated in simulated intratubular concentrations of acyclovir and sulfamethoxazole, agreed with clinical data on tubular precipitation and crystal-induced acute kidney injury. This study represents the first systematic evaluation of the ability of the mechanistic kidney model to capture the impact of Urine flow and Urine pH on CLR and drug tubular concentrations with the aim of facilitating refinement of IVIVE-based mechanistic prediction of renal excretion.
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assessment of in vivo cyp2d6 activity differential sensitivity of commonly used probes to Urine pH
The Journal of Clinical Pharmacology, 2004Co-Authors: Mahmut Ozdemir, Kim H Crewe, Geoffrey T Tucker, Amin RostamihodjeganAbstract:: Drug/metabolite ratios (MRs) are used as in vivo markers of enzyme activity. The ratios are potentially confounded by the renal clearance of the drug (Urine-based MRs) or metabolite (plasma-based MRs). The authors have investigated the relative sensitivity of urinary MR of 3 in vivo probe substrates of CYP2D6 debrisoquine (DB), dextromethorpHan (DM), and metoprolol (MP) to changes in Urine pH. Three groups of healthy volunteers each comprising 12 individuals were given DB (10 mg), DM (25 mg), or MP (100 mg) on 3 occasions. In 1 study arm, Urine was acidified by the oral intake of ammonium chloride; in another, it was alkalinized by intake of sodium bicarbonate; and in the third, Urine pH was uncontrolled. Urinary MP/alpHa-hydroxy-MP, DM/dextrorpHan, and DB/4-hydroxy-DB ratios were calculated. The mean(geo) MR for DB was not significantly different in any of the study arms, whereas those for MP and DM were significantly different under acidified and alkalinized Urine conditions compared to uncontrolled Urine pH (P < .01) and were correlated with Urine pH (P < .001). Without control of Urine pH, in vivo estimates of CYP2D6 metabolic activity are likely to be less precise using DM or MP as probe substrates compared to DB. Although this is unlikely to cause any problem in distinguishing the large functional differences in CYP2D6 in poor metabolizer (PM) and extensive metabolizer (EM) pHenotypes, this may contribute to difficulties in differentiating in vivo metabolic activity among allelic variants within the overall CYP2D6 EM pHenotype using MP or DM. However, because DB is not available in many countries (eg, United States), alternative in vivo markers of CYP2D6 with low sensitivity to Urine pH should be sought.
