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PubMed2005

Antioxidative effects of tetramethylpyrazine on acute ethanol-induced lipid peroxidation.

Acute p.o. administration of 99.5% ethanol (0.1 ml) to fasted mice produced heart toxicity. Pretreatment with p.o. administration of tetramethylpyrazine (TMP) could prevent such toxicity effectively and dose-dependently. The maximal antioxidative effect against 99.5% ethanol-induced heart toxicity could be observed at 1 hour after TMP administration. In order to further investigate the heart protective mechanism of TMP, both lipid peroxidation level in vivo and superoxide scavenging activity were conducted. TMP exhibited a dose-dependently anti-lipid peroxidation effect in mice heart homogenate, and results indicated that 99.5% ethanol-induced intoxicated mice hearts have higher malonic dialdehyde (MDA) levels compared with those in TMP administrated mice hearts. These results suggest that the potentially heart protective mechanism of TMP could be contributed, at least in part, to its prominent anti-lipid peroxidation and anti-free radical formation effects, hence it could protect the heart from lipid peroxidation-induced heart toxicity.

Animals↗
PubMed1994

X-linked hypophosphatemic Gy mice: renal tubular maximum for phosphate vs. brush-border transport after low-P diet.

We examined the effect of the X-linked hypophosphatemic Gy mutation on the maximal renal tubular reabsorption of phosphate (TmP) and compared the effects of phosphate deprivation on both TmP and Na(+)-dependent phosphate transport in renal brush-border membrane vesicles (BBMV). Adult female normal and Gy mice were fed a control (1.0% P) or low-phosphate (0.03% P) diet for 5 days. For TmP measurement, anesthetized mice were infused intravenously with [3H]inulin and increasing increments of phosphate (0, 0.27, 0.54, and 1.08 mumol/min). TmP was significantly reduced in Gy mice on the control diet. Normal mice responded to the low-phosphate diet by raising their TmP [2.35 +/- 0.12 (n = 9) vs. 3.71 +/- 0.16 (n = 9) mumol/ml glomerular filtrate, mean +/- SE, P < 0.001], whereas in Gy mice, the change was not significant [1.46 +/- 0.10 (n = 10) vs. 1.70 +/- 0.11 (n = 10)]. In contrast, Gy mice did respond to phosphate restriction by increasing the initial-rate Na(+)-dependent phosphate transport in the renal BBMV [314 +/- 11 (n = 5) vs. 1,105 +/- 157 (n = 5) pmol.mg protein-1.6 s-1, P < 0.01] as did normal mice [583 +/- 64 (n = 5) vs. 1,692 +/- 203 (n = 5) pmol.mg protein-1.6 s-1, P < 0.01]. In conclusion, the adaptive increase in Na(+)-phosphate cotransport in the brush-border membrane of the proximal tubule is not sufficient for the overall increase in TmP in the whole kidney in response to dietary phosphate deprivation.

Absorption↗
PubMed2002

Antimicrobial susceptibility of Gram-negative uropathogens isolated from obstetric patients.

OBJECTIVE: To evaluate the antimicrobial susceptibility of Gram-negative uropathogens isolated from pregnant women. METHODS: We performed a snapshot cohort study of women receiving care in the University of Florida prenatal clinics during March 2000. Subjects with asymptomatic bacteriuria or cystitis were identified and the antimicrobial susceptibility of each pathogen was recorded. Data were analyzed using chi-square, Fisher's exact test and ninety-five percent confidence intervals, as appropriate. RESULTS: Ninety-five positive cultures were identified. Isolates were more often susceptible to trimethoprim-sulfamethoxazole (TMP-SMX) (87%) and nitrofurantoin (89%) than to ampicillin (72%) (p < 0.03). Escherichia coli accounted for 71 (75%) cases and was more often susceptible to nitrofurantoin (100%) than to TMP-SMX (87%) (p < 0.01). Proteus isolates were all susceptible to TMP-SMX and resistant to nitrofurantoin (p < 0.01). CONCLUSIONS: Both TMP-SMX and nitrofurantoin are superior to ampicillin for empiric treatment of lower urinary tract infection in pregnant women. Nitrofurantoin is superior to TMP-SMX for treatment of infections caused by E. coli. For suspected or confirmed cases caused by Proteus organisms, TMP-SMX is the preferred agent.

Adult↗
PubMed2005

Effect of trimethoprim-sulfamethoxazole on Na and K+ transport properties in the rabbit cortical collecting duct perfused in vitro.

BACKGROUND: In this study, the membrane mechanisms of hyperkalemia caused by trimethoprim-sulfamethoxazole (TMP-SMX) combination antibiotics were assessed in the cortical collecting duct (CCD). METHODS: We used the microelectrode technique and flux measurements, and examined the effects of TMP and SMX on electrical properties of the apical and basolateral membranes in the rabbit CCD perfused in vitro. RESULTS: TMP in the lumen caused increases in apical membrane voltage, fractional apical membrane resistance (fRA), and transepithelial resistance (RT), all effects which were completely inhibited by luminal amiloride, but not by luminal Ba2+. The luminal TMP inhibited both net Na+ reabsorption and K+ secretion in the CCD. TMP in the bath slightly but significantly depolarized transepithelial voltage and basolateral membrane voltage without influencing fRA or RT. SMX in the lumen or bath had no effect on barrier voltages or resistances. CONCLUSION: TMP mainly acts on the apical membrane of the CCD, inhibits the amiloride-sensitive macroscopic Na+ conductance in this membrane, and thereby decreases the net driving force for K+ exit across the membrane, resulting in an inhibition of K+ secretion. SMX in the lumen or bath had no effect on the CCD.

Animals↗
PubMed1984

Properties of brodimoprim as an inhibitor of dihydrofolate reductases.

Based on both IC50 and Ki values, brodimoprim (BDP) was often found to be two- to threefold more effective than trimethoprim (TMP) against a great variety of different bacterial dihydrofolate reductases (DHFR). In all cases BDP was found to be a reversible, tight-binding inhibitor. The higher affinity for enzymes relatively insensitive to TMP, like those of Nocardia, which is paralleled by higher in vitro activity, may be therapeutically useful. BDP also often inhibited plasmid-coded, TMP-resistant DHFRs, as well as altered chromosomal TMP-resistant DHFRs at lower concentrations than TMP did, this property, however, being therapeutically irrelevant. A higher affinity was also observed for eucaryotic DHFRs, the specificity, however, remaining similar to that of TMP.

Animals↗
PubMed1986

Histopathology and cell proliferation induced by 2,2,4-trimethylpentane in the male rat kidney.

Unleaded gasoline causes acute and chronic nephrotoxicity and renal tumors in male rats, but not female rats or mice of either sex. An active nephrotoxic component of unleaded gasoline has been identified as 2,2,4-trimethylpentane (TMP). The first objective of this study was to characterize light microscopic renal lesions induced in male F344 rats by a 21-day gavage regimen of 50 to 500 mg/kg TMP. The second objective was to localize and quantitate sites of renal cell proliferation induced by the same TMP dose regimens using histoautoradiographic analysis after [3H]thymidine incorporation. Light microscopic lesions in the proximal convoluted tubule consisted of protein droplet and crystalloid body accumulation, degeneration, and necrosis, and were similar to lesions noted in previous inhalation and gavage studies with other hydrocarbon compounds. The above renal lesions were not dose-related, although tubular dilation of thin limb segments with granular cell debris was dose-related. In cell proliferation studies TMP induced a non-dose-related five- to sixfold increase in the labelling index of the same proximal convoluted tubule portions (P2 segment) that contained severe crystalloid body accumulation, degeneration, and necrosis. Less pronounced, but statistically significant (p less than or equal to 0.05), increases in cell proliferation were also observed in other nephron segments, indicating a generalized regenerative response of the kidney to TMP. The cytotoxic and regenerative renal effects of TMP administered by gavage suggest that similar mechanisms may be involved in the induction of kidney tumors in male rats following chronic inhalation exposure to unleaded gasoline.

Animals↗
PubMed2006

Crystal engineering of analogous and homologous organic compounds: hydrogen bonding patterns in trimethoprim hydrogen phthalate and trimethoprim hydrogen adipate.

BACKGROUND: Trimethoprim [2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine] is an antifolate drug. It selectively inhibits the bacterial dihydrofolate reductase (DHFR) enzyme. RESULTS: In the crystal structures of trimethoprim (TMP)-hydrogen phthalate (1) and trimethoprim-hydrogen adipate (2), one of the N atoms of the pyrimidine ring is protonated and it interacts with the deprotonated carboxylate oxygens through a pair of nearly parallel N-H...O hydrogen bonds to form a fork-like interaction. In the compound 1, the pyrimidine moieties of the TMP cations are centrosymmetrically paired through a pair of N-H...N hydrogen bonds involving 4-amino group and the N (N3) atom of the pyrimidine rings to form a 8-membered hydrogen bonded ring [R2(2)(8)]. The 4-amino group of one TMP moiety and 2-amino group of another TMP moiety (both moieties are members of a base pair) are bridged by the carbonyl oxygen of the phthalate moiety through N-H...O hydrogen bonds forming 8-membered hydrogen-bonded ring [R2(2)(8)]. The characteristic hydrogen-bonded rings observed in the structure aggregate into a supramolecular ladder consisting of a pair of chains, each of which is built up of alternate TMP and hydrogen phthalate ions. In the compound 2, two TMP cations and two hydrogen adipate anions are arranged about an inversion center so that the complementary DDAA (D = donor, A = acceptor) arrays of quadruple hydrogen-bonding patterns are formed. The head-to-tail arrangement of the hydrogen adipate ions leads to a hydrogen-bonded supramolecular chain. From crystal engineering point of view, it is interesting to note that the compound 1 has a hydrogen-bonded network remarkably identical with its aliphatic analogue, trimethoprim hydrogen maleate. Similarly the compound 2, resembles its homolog trimethoprim hydrogen glutarate. CONCLUSION: In the crystal structure of trimethoprim hydrogen phthalate, the hydrogen-bonded network is remarkably identical with its aliphatic analogue, trimethoprim hydrogen maleate. Similarly in the crystal structure of trimethoprim hydrogen adipate the hydrogen bonded network resembles its homolog trimethoprim hydrogen glutarate.

Journal Article↗
PubMed2005

Transient psychosis in an immune-competent patient after oral trimethoprim-sulfamethoxazole administration.

We describe a rare adverse reaction to trimethoprim-sulfamethoxazole (TMP-SMX; Septra, Bactrim) in an immune-competent female adolescent. She was prescribed TMP-SMX for a urinary tract infection, which she had developed while being treated in the hospital for an extensive leg cellulitis. Shortly after receiving her third dose of TMP-SMX, she developed an acute altered mental status with agitation as well as vivid visual and auditory hallucinations. After prompt discontinuation of TMP-SMX, the patient slowly began to improve and was able to return to her baseline mental status within 10 days. No residual mental status changes were present. Despite the recent emergence of multidrug-resistant bacterial pathogens, TMP-SMX, one of the first-generation broad-spectrum antibiotics, continues to be widely prescribed, in part because of its low cost and its easy availability. It is generally well tolerated and is associated with relatively few adverse effects. More common toxicities associated with TMP-SMX include hypersensitivity reactions, bone marrow suppression, and gastrointestinal side effects. Central nervous system toxicity is very rare; when reported, it has been in an immune-compromised or an elderly patient.

Acute Disease↗
PubMed2005

Change in intrathoracic pressure in rats with spontaneous and controlled ventilation during microgravity by parabolic flight.

We previously reported that the intrathoracic pressure (ITP) decreases and the transmural pressure of the aortic wall (TMP) increases during 4.5 s of microgravity (muG) induced by free drop. To examine the ITP response to a longer period of muG in the absence of the respiratory rate (RR) decrease, i.e., bradypnea, which occurs at the onset of muG, we measured the aortic blood pressure at the diaphragma level (AP) and ITP. We then calculated the TMP at the aortic arch level during 20 s of muG induced by parabolic flight in anesthetized rats (n = 7) with either spontaneous ventilation (SPN-V) or controlled ventilation (CONT-V). In the SPN-V group, the bradypnea was observed in all rats after the onset of the muG (RR change -13.9 +/- 2.9/min). The ITP during muG (-9.3 +/- 0.9 mmHg) was significantly lower than that during 1 G (-7.7 +/- 0.9 mmHg), and the TMP was significantly increased during muG (112 +/- 6 mmHg) compared to 1 G (103 +/- 5 mmHg). Similar changes in ITP and TMP were observed in the CONT-V group: During muG and 1G, respectively, the ITP was -8.4 +/- 0.6 mmHg and -5.9 +/- 0.7 mmHg, and the TMP was 112 +/- 6 mmHg and 101 +/- 6 mmHg, whereas no change in RR was observed because of the controlled ventilation. These results show that the ITP decreases and the TMP increases during muG, and they are not affected by a disturbance of respiratory rhythm.

Anesthesia↗
PubMed1986

Significance of the sulfonamide component for the clinical efficacy of trimethoprim-sulfonamide combinations.

The reasons for combining trimethoprim (TMP) with sulfonamides (SUL) are still mainly theoretical but are supported by results from experimental infections and treatment of specific pathogens in humans, such as Branhamella catarrhalis, Neisseria gonorrhoeae, Brucella, Nocardia asteroides and perhaps Bordetella pertussis and Chlamydia trachomatis. Addition of SUL to TMP confers a therapeutic advantage also in patients with complicated urinary tract infection but probably not in young women with acute cystitis. Conditions that may enable TMP-SUL synergy in vivo can be expected to occur only in occasional cases of infection due to staphylococci, streptococci, Haemophilus or enteric bacteria. This fact together with ethical problems and availability of alternative therapies make further evaluations of the clinical significance of the SUL component of TMP-SUL very difficult. Although the use of TMP alone has shown promise in exacerbations of chronic bronchitis the role of the SUL component in TMP-SUL treatment of infections outside the urinary tract remains to be defined in comparative clinical trials.

Aged↗
PubMed1995

Randomized study of sulfamethoxazole-trimethoprim versus aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with AIDS.

In a prospective, randomized open-label trial, the efficacy of sulfamethoxazole-trimethoprim (SMX-TMP) 400/80 mg b.i.d. was compared with the efficacy of aerosolized pentamidine (AP) 60 mg every 2nd week as secondary prophylaxis (SP) against recurrence of Pneumocystis carinii pneumonia (PCP) in AIDS patients. 94 patients participated in the study, 47 in each group. The patients were observed for a mean period of 17.2 months. PCP recurred in the AP group in 8 cases, while 1 relapse occurred in the SMX-TMP group. The one-year cumulative relapse rate was 9.0% (95% CI 0-19%) in the AP group compared with 2.4% (95% CI 0-8%) in the SMX-TMP group (p < 0.05). The odds ratio was 4.2 (95% CI 0.5-39.8) in favour of SMX-TMP. Furthermore, we found a tendency towards a protective effect against toxoplasmosis in the SMX-TMP group, though there was no difference in survival between the two groups. There was no statistical difference in frequency of crossover from one therapy form to the other. Based on these data we recommend SMX-TMP for secondary PCP prophylaxis.

AIDS-Related Opportunistic Infections↗
PubMed1988

Intestinal transport of thiamin and thiamin monophosphate in rat everted jejunal sacs: a comparative study using some potential inhibitors.

Rat everted jejunal sacs were incubated for 15 and 30 min at 37 degrees C in oxygenated Krebs-Henseleit buffer, pH 7.4, containing 0.2 microM [3H]-thiamin (3H-T) or [3H]-thiamin monophosphate (3H-TMP) with and without 10 mM 1-phenylalanine (PAL) or 2.5 mM levamisole (LEV). The concentrations of 3H-T and its phosphoesters in sac wall and serosal fluid were determined by a radiometric method after electrophoretic separation. In separate experiments, thiamin pyrophosphokinase (TPKase) and thiamin pyrophosphatase (TPPase) activities were determined in mucosal scrapings, with and without PAL or LEV, by using a radiometric and a colorimetric method, respectively. 3H-TMP was transported partly unchanged by an active mechanism similarly to 3H-T, but less efficiently. During transport, 3H-TMP was also enzymatically transformed to thiamin (T) and thiamin pyrophosphate, which accumulated in the tissue. In the serosal fluid, the concentration of 3H-TMP exceeded that of 3H-T. Presence of PAL or LEV with 3H-T or 3H-TMP in the incubation medium reduced the serosal transport and the tissue content of T compounds. LEV caused a dose-dependent inhibition of TPKase without affecting TPPase, whereas PAL inhibited both activities to about the same extent. These results indicate that the transport of TMP involves a number of different processes similar to those responsible for T transport. The effects of PAL and LEV underline the importance of phosphorylation-dephosphorylation coupling.

Animals↗
PubMed1981

Epidemiologic features of urinary infections due to enterobacteriaceae resistant to nalidixic acid and trimethoprim.

For a period of one year we identified all urinary isolates of Enterobacteriaceae resistant to either nalidixic acid (NA) or trimethoprim (TMP). Host and organism characteristics associated with the occurrence of 68 NA and 61 TMP-resistant isolates were compared with 61 matched antimicrobial-susceptible controls. Minimum inhibitory concentrations to NA and TMP were carried out on all isolates, Escherichia coli isolates were biotyped and TMP-sulfamethoxazole (SMX) synergy studies were performed on TMP-resistant isolates. Study patients were reviewed with regard to age, renal function, presence of structural urinary tract abnormality, history of antimicrobial treatment and persistence of study strains within the urinary tract. Resistance to both drugs was associated with prior treatment with the relevant antimicrobial and with underlying urinary tract abnormality. No association was noted between resistance and patient age or renal function. Once resistant organisms infected an abnormal urinary tract, they were able to persist almost indefinitely. Patients with persistent urinary infections associated with structural urinary tract abnormality account for most NA or TMP-resistant infections in our hospital and constitute an identifiable group in whom the therapeutic usefulness of these drugs is limited.

Adult↗
PubMed1983

Serum and saliva concentrations of sulfamethoxazole and trimethoprim in adults and children: relation between saliva concentrations and in vitro activity against nasopharyngeal pathogens.

The combination sulfamethoxazole/trimethoprim (SMX/TMP) was given orally to 4 healthy adult volunteers in mean daily doses of 23.0/4.6 mg/kg body weight for 6 days. The serum and saliva concentrations of the drugs were assayed on days 1, 3 and 6. On the first day (0-12 h) there was no measurable concentration of SMX in the saliva. On days 3 and 6 the mean peak levels of SMX in saliva were 7.8 and 9.8 micrograms/ml, i.e. 8-9% of the corresponding mean peak serum levels. In contrast, the concentrations of TMP in saliva were more than twice as high as those in serum. The mean SMX/TMP ratios in saliva days 3 and 6 were 1.3 and 1.4, respectively, i.e. approximately one-twentieth of the mean SMX/TMP ratios in serum. SMX/TMP was also administered to children with serous otitis media. The drug concentrations in saliva were assayed 2-3 h after administration on days 6 and 9 of a 10-day course, with a mean daily dose of 34.5/6.9 mg/kg body weight. The mean saliva concentration of SMX in the children was slightly higher than in adults and the mean TMP concentration about half of that in adults. The mean SMX/TMP ratio in the children's saliva was 4.2. The in vitro activity of SMX/TMP 20:1 and 4:1 was determined against H. influenzae, D. pneumoniae, B. catarrhalis and group A streptococci. H. influenzae, D. pneumoniae and group A streptococci were found more susceptible to TMP than to SMX, while the reverse was true for B. catarrhalis. In the 3 former, the potentiation of SMX by TMP was more pronounced than was the potentiation of TMP by SMX, while the opposite was recorded for B. catarrhalis. The most beneficial effect of the SMX/TMP combination against nasopharyngeal pathogens was recorded for B. catarrhalis and the weakest effect for H. influenzae and group A streptococci. With the exception of B. catarrhalis, the administration of TMP alone to adults may be just as effective against nasopharyngeal pathogens as is the SMX/TMP combination in children.

Adult↗
PubMed1993

[Prophylactic effects of trimethoprim-sulfamethoxazole in Toxoplasma-infected mice].

This study was performed to evaluate the prophylactic effects of trimethoprim-sulfamethoxazole (TMP-SMZ) in mice experimentally infected with virulent RH strain and avirulent Beverley strain of T. gondii. The mice infected with 1 x 10(5) tachyzoites were used in the measurement of mean survival days, and the mice infected with 10 cysts were used in the titrations of specific antibodies and enumeration of brain cysts. Mean survival days of mice were significantly increased in mice treated with TMP-SMZ as compared with spiramycin-treated and untreated control group. Mean survival days and survival rates of mice were increased according to the increment of dosages, and TMP-SMZ protected 100% of mice after fifteen daily dose of 24 mg/mouse or more administered orally. Toxoplasma-specific serum IgG and IgM antibody titers were significantly lower in mice treated with TMP-SMZ than those of spiramycin-treated and untreated control group. Toxoplasma cysts were not found in mice treated with TMP-SMZ at a dose of 24 mg/mouse or more per day, but the group of spiramycin treatment and untreated controls were found in the brain from 20 days after infection. The present results revealed that TMP-SMZ can be used as a prophylactic agent against murine toxoplasmosis after intraperitoneally challenges with the virulent or avirulent strain of T. gondii.

Animals↗
PubMed2000

Pharmacokinetics of traditional Chinese syndrome and recipe: a hypothesis and its verification (I).

AIM:To propose a hypothesis defining the absorption, distribution, metabolism and elimination of traditional Chinese recipe (TCR)component in blood of healthy subjects and patients, and estimate its correctness.METHODS:The pharmacokinetics (PK) of same dose of drug was studied in the animal model of traditional Chinese syndrome (S)and healthy animals. The classification, termi-nology, concept and significance of the hypothesis were set forth with evidence provided in the present study. The hypotheses consisted of traditional Chinese syndrome PK (S-PK) and traditional Chinese recipe PK (R-PK). Firstly, the observed tetramethylpyrazine (TMP) PK in healthy, chronically reserpinized rats (rat model of spleen deficiency syndrome, RMSDS) and RMSDS treated with Sijunzi decoction (SJZD) for confirmation were used to verify S-PK; secondly, the ferulic acid (FA) PK in healthy and high molecular weight dextran (HMWD)-induced rabbit model with blood stasis syndrome (RDBSS) was also used to verify S-PK; and lastly, TMP PK parameters in serum of healthy rats after orally taken Ligusticum wallichii (LW), LW and Salvia miltiorrhiza (LW&SM) decoctions were compared to verify R-PK.RESULTS:The apparent first-order absorption Ka,(13.61 plus minus 2.56)h(-1) ,area under the blood drug concentration-time curve AUC, (24.88 plus minus 9.76)&mgr;gcenter doth(-1)mL(-1) , maximum drug concentration C(max), (4.82 plus minus 1.23)&mgr;gcenter dotmL(-1) of serum TMP in RMSDS were increased markedly(P< 0.05) compared with those Ka = (5.41 plus minus1.91)h(-1), AUC = (5.20 plus minus 2.57)&mgr;gcenter doth(-1)center dotmL(-1), C(max) = (2.33 plus minus 1.77)&mgr;gcenter dotmL(-1) of healthy rats (HR). The apparent first-order rate constant for alpha and beta distribution phase alpha = (0.38 plus minus 0.09)h(-1), beta = (0.06 plus minus 0.03)h(-1) , the apparent first-order intercompartmental transfer rate constants K10 = (0.24 plus minus 0.07)h(-1), K(12) = (0.11 plus minus 0.02)h(-1), K(21) = (0.11 plus minus 0.02)h(-1) of serum TMP in RMSDS were decreased significantly (P <0.01) compared with those K(10) = (0.88 plus minus 0.20)h(-1), K(12) = (1.45 plus minus 0.47)h(-1), K(21) = (0.72 plus minus 0.22)h(-1) of HR. However, no apparent differences occurred between HR and RMSDS treated with SJZD. The serum FA concentration and its AUC (5.6690 plus minus 2.3541)&mgr;gcenter doth(-1)center dotmL(-1) in RMBSS were also higher than those AUC =(2.7566 plus minus0.8232)&mgr;gcenter doth(-1)center dotmL(-1) of healthy rabbits (P <0.05). The Ka (11.51 plus minus 2.82)h(-1), AUC (0.84 plus minus0.17)&mgr;gcenter doth(-1)center dotmL(-1) of LW & SM-derived TMP in serum were much lower (P <0.05) than those Ka = (19.58 plus minus 4.14)h(-1),AUC = (1.27 plus minus 0.26)&mgr;gcenter doth(-1)center dotmL(-1) of LW-derived TMP in serum after oral decoctions.CONCLUSION:The SDS and blood stasis syndrome state could affect significantly the pharmacokinetic parameters of drugs and the abnormal SDS pharmacokinetic parameters could be normalized by SJZD. The combination of Chinese medicine in TCR could reciprocally affect the pharmacokinetic parameters of other components absorbed into the systemic circulation. These results support the S and R-PK hypothesis.

Journal Article↗
PubMed1993

Trimethoprim-sulfamethoxazole induces reversible hyperkalemia.

OBJECTIVE: To determine the effect of trimethoprimsulfamethoxazole (Tmp-Smx) on serum potassium concentration. DESIGN: Retrospective cohort study. SETTING: An urban teaching hospital. PATIENTS: Fifty-one persons hospitalized for symptomatic infection with human immunodeficiency virus (HIV). Twenty-five patients who were taking high-dose Tmp-Smx (trimethoprim 20 mg/kg per day; sulfamethoxazole, 100 mg/kg per day) for Pneumocystis carinii pneumonia were the study group. Twenty-six patients who had not received the drug were the control group. Patients who received potassium supplements, those taking medications known to alter potassium homeostasis or renal function, or those with a serum creatinine level more than 186 mumol/L were excluded. MEASUREMENTS AND MAIN RESULTS: Serum potassium concentration in the study group was 4.1 +/- 0.1 mmol/L (mean +/- SE) and increased by 1.1 mmol/L (Cl, 0.8 to 1.5 mmol/L) (P < 0.0001) 9.8 +/- 0.5 days after starting Tmp-Smx therapy. Patients followed longitudinally showed a progressive increase in serum potassium levels during therapy and a progressive decline after discontinuing Tmp-Smx. Blood urea nitrogen and serum creatinine levels increased mildly from 4.3 +/- 0.5 mmol/L and 85 +/- 6 mumol/L to 6.4 +/- 0.7 mmol/L and 113 +/- 8 mumol/L, respectively. The serum potassium level in the control group was 4.3 +/- 0.1 mmol/L and remained unchanged during hospitalization. CONCLUSIONS: High-dose Tmp-Smx therapy used for the treatment of P. carinii pneumonia in HIV-infected patients leads to an increase in the serum potassium concentration and may result in life-threatening hyperkalemia. Patients receiving high doses of Tmp-Smx require close monitoring of their serum potassium concentration, particularly 7 to 10 days after the start of therapy.

AIDS-Related Opportunistic Infections↗
PubMed2001

Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections.

Community-acquired urinary tract infections (UTIs) are among the most common bacterial infections in women. Therapy for these infections is usually begun before results of microbiological tests are known. Furthermore, in women with acute uncomplicated cystitis, empirical therapy without a pretherapy urine culture is often used. The rationale for this approach is based on the highly predictable spectrum of etiologic agents causing UTI and their antimicrobial resistance patterns. However, antimicrobial resistance among uropathogens causing community-acquired UTIs, both cystitis and pyelonephritis, is increasing. Most important has been the increasing resistance to trimethoprim-sulfamethoxazole (TMP-SMX), the current drug of choice for treatment of acute uncomplicated cystitis in women. What implications do these trends have for treatment of community-acquired UTIs? Preliminary data suggest that clinical cure rates may be lower among women with uncomplicated cystitis treated with TMP-SMX when the infecting pathogen is resistant to TMP-SMX. Women with pyelonephritis also have less bacterial eradication and lower clinical cure rates when treated with TMP-SMX for an infection that is resistant to the drug. Therefore, in the outpatient setting, identifying risk factors for TMP-SMX resistance and knowing the prevalence of TMP-SMX resistance in the local community are important steps in choosing an appropriate therapeutic agent. When choosing a treatment regimen, physicians should consider such factors as in vitro susceptibility, adverse effects, cost-effectiveness, and selection of resistant strains. Using a management strategy that takes these variables into account is essential for maintaining the safety and efficacy of treatment for acute UTI.

Anti-Infective Agents, Urinary↗