Annals of Pharmacotherapy

To determine the effect on the relative bioavailability (Fr) of a staggered single dose of ciprofloxacin given two hours after a morning dose of calcium carbonate given three times daily over the three previous days.

Thirteen male volunteers participated in this randomized, nonblinded, crossover investigation; 12 subjects were included in the final analysis.

Data collection and ciprofloxacin administration occurred at Albany Medical Center, a tertiary-care teaching institution. Calcium carbonate administration was on an outpatient basis.

For 12 volunteers, the mean ± SD Fr of ciprofloxacin staggered with calcium was 0.87 ± 0.23 (noncompartmental model) and 0.98 ± 0.27 (compartmental model). Other statistically significant findings were a decrease in the time to maximum concentration of ciprofloxacin staggered with calcium in serum compared with ciprofloxacin alone (from 1.76 ± 0.54 to 1.23 ± 0.52 h in the noncompartmental model; p<0.05), and a decrease in the same parameter (from 1.92 ± 0.96 to 0.77 ± 0.53 in the compartmental model; p<0.005). Maximum concentration of ciprofloxacin staggered with calcium was decreased in the noncompartmental model compared with ciprofloxacin alone (from 2.11 ± 0.72 to 1.60 ± 0.33, respectively; p<0.05). The elimination half-life and area under the concentration-time curve of ciprofloxacin were not significantly altered.

Repeated doses of calcium carbonate, administered two hours before ciprofloxacin, did not significantly alter the Fr of this fluoroquinolone.

To determine the effect on male sexual function of initiating any one of the cardiovascular medications most frequently prescribed at our institution.

Men were surveyed via telephone when they received a new prescription for hydrochlorothiazide, furosemide, lisinopril, verapamil, nifedipine, or diltiazem, and after 30 days of daily medication ingestion. To assess Hawthorne effect, men who had no change to their medication regimen also were surveyed at the time of medication refill for maintenance therapy and 30 days later.

Community-dwelling male veterans who received a single new prescription between January 1 and April 1, 1992 (n=134).

Responses to questions about sexual interest, erectile function, orgasmic ability, and sexual satisfaction.

Men who had no change to their medication regimen showed no change in sexual interest, erectile function, orgasmic ability, or satisfaction. Hydrochlorothiazide was associated with decreased orgasmic ability (p=0.008). Although none of the other changes were statistically significant (p<0.05), both nifedipine and diltiazem showed a trend toward improved sexual function.

Hydrochlorothiazide may be associated with anorgasmia. More study is needed to determine if nifedipine and diltiazem improve erectile function. Furosemide, lisinopril, and verapamil likely have no effect on sexual function.

One-compartment pharmacokinetic equations are adequate to perform clinical dosing adjustments for aminoglycoside monitoring. This article describes the Fuller-Goldman (FG) method, an alternative method of aminoglycoside dosage adjustment after serum concentrations have been obtained. The FG method uses pharmacokinetic principles, but does not use standard pharmacokinetic equations (SPE) for aminoglycoside dosage adjustment. A comparison of the FG method to SPE is also presented.

Information was obtained from pharmacokinetic textbooks and references using basic pharmacokinetic concepts. Forty sets of peak and trough serum drug concentrations were randomly chosen, retrospectively, from routine pharmacokinetic service data. All of the patients were men with a variety of infectious diseases and cared for on general surgical and medical floors, intensive care units, and a spinal cord injury unit.

No studies have previously been published using this dosing method.

Peak and trough data were extracted from routine pharmacokinetic monitoring forms kept by the coordinator of the Pharmacokinetic Monitoring Service at the Department of Veterans Affairs Medical Center.

The FG method is characterized by assumptions and limitations similar to those of standard pharmacokinetic dosing methods. Forty sets of data were evaluated using both the FG method and SPE. These data were analyzed using mean percent differences of projected dosages and projected half-lives (t¹/2s) as measures of the average magnitude of the discrepancy between the two methods. Ninety-five percent confidence intervals for mean percent differences also are provided.

The FG method overestimated by 10.18 percent the dosage recommendations of the SPE method. This method also underestimated t¹/2 by 2.96 percent, compared with SPE. The FG method is a viable alternative aminoglycoside dosing technique that requires one to use learned pharmacokinetic concepts.

To present a case of Rhodococcus equi (RE) pneumonia and discuss its pathophysiology and treatment.

An HIV-positive patient presented with pneumonia. A lung biopsy was performed after sputum and thoracentesis cultures failed to identify a pathogen. The lung biopsy revealed an unidentifiable, diphtheroid-like, gram-positive rod. A bronchoscopy performed five days after the lung biopsy produced the same diphtheroid-like, gram-positive rod. The patient was treated with several injectable antibiotics, but emergence of resistance to two of the antibiotics was suspected. Two weeks after the bacterial isolate was sent to a reference laboratory, it was identified as RE. The patient was discharged on oral antibiotics and experienced no recurrence of RE pneumonia.

RE can be difficult to identify in the microbiology laboratory, or it may be assumed to be a colonizing diphtheroid. The isolation of difficult-to-identify, gram-positive rods, or diphtheroids, from a pulmonary source in a patient with decreased cell-mediated immunity should cause one to suspect RE. RE has been noted to develop resistance to beta-lactam antibiotics during therapy. A prolonged course of combination antibiotic therapy directed at the intracellular component of infection is necessary.

To compare the safety and efficacy of intravaginal clindamycin 2% cream with placebo in nonpregnant women with bacterial vaginosis.

A randomized, double-blind, placebo-controlled clinical trial.

Ambulatory patients in the general community.

Two hundred fifteen nonpregnant outpatients with a diagnosis of bacterial vaginosis were entered into this study. Of the 134 evaluable patients, 65 received clindamycin and 69 placebo. Demographic parameters were comparable between the two treatment groups.

Study subjects were equally randomized to receive either 5 g of clindamycin 2% vaginal cream or placebo cream for seven nights.

Clinical and microbiologic follow-up evaluations were scheduled for 5–10 days and 25–39 days posttreatment. Patients were interviewed about signs and symptoms, adverse events, and compliance. Diagnostic examinations were performed.

Clinical success rates (cure and improvement) occurred in 50 of 65 patients who received clindamycin (77 percent) and 17 of 69 patients who received placebo (25 percent) by the first posttreatment visit (p<0.001). Microbiologic cures or improvement were observed in 59 of the 65 patients treated with clindamycin (91 percent) compared with 20 of 69 placebo-treated patients (29 percent) (p<0.001). At the end of the study, clinical and microbiologic cures or improvement were evident in 45 of 57 (79 percent) and 37 of 57 clindamycin-treated patients (65 percent), respectively, and 18 of 51 (35 percent) and 14 of 51 (28 percent) of the placebo-treated patients, respectively. The success rates with clindamycin 2% cream were statistically higher than those with placebo. The adverse-effect profiles in the two groups were similar and no serious adverse effects were reported. Patients who received clindamycin had a statistically higher incidence of nonbacterial vaginitis/cervicitis (18.5 vs. 7.5 percent, p=0.003).

Intravaginal clindamycin 2% cream appears to be an effective and safe treatment of symptomatic bacterial vaginosis in nonpregnant women.

To investigate a correlation between the elimination rate constants (K_e) of aminoglycosides (AG) and vancomycin; to investigate the correlation between actual K_e and creatinine clearance (Cl_cr) for AG versus vancomycin; to investigate the calculated versus actual K_e for AG and vancomycin; and to investigate a correlation between volumes of distribution (V_d) between AG and vancomycin.

Retrospective data collection.

Patients in our institution who received AGs or vancomycin concomitantly or within six weeks of each other were identified retrospectively. Patient subpopulations were identified and analyzed collectively as well as individually. Steady-state serum concentrations of AG and vancomycin (more than four half-lives) were obtained and kinetic parameters (K_e‘ V_d) were calculated using first-order pharmacokinetic equations. Linear regression was used to determine correlation coefficients.

In the total population and all subpopulations, the correlation between K_e of AG and vancomycin was superior to the correlation between K_e and Cl_cr. The correlations (r²) between K_e for AG and vancomycin in the total, general medicine, oncology, and intensive care units (ICU) populations were 0.572, 0.878, 0.349, and 0.561, respectively. The correlations (r²) between K_e and Cl_cr for AG in the total, general medicine, oncology, and ICU populations were 0.235, 0.430, 0.005, and 0.238, respectively. The correlations (r²) between K_e and Cl_cr for vancomycin in the total, general medicine, oncology, and ICU populations were 0.300, 0.407, 0.055, and 0.309, respectively.

The correlation between K_e of AG and vancomycin may be beneficial for predicting K_e of vancomycin when AG concentrations have already been obtained or vice versa, and may give more accurate estimations of dosing intervals and require less time adjusting, ordering, and interpreting concentrations and dosages.

To evaluate the in vivo radical scavenger activity of vitamin E, vitamin C, and beta carotene on erythrocyte membranes.

A prospective, open trial without placebo.

Department of Clinical Pharmacy.

Ten healthy volunteers being supplemented with beta carotene, vitamin E, and vitamin C.

Erythrocytes were incubated in water bath with 2,2′ azobis (2 amidinopropane) hydrochloride (AAPH). AAPH decomposes spontaneously at 37 °C to generate free radicals inducing membrane cellular damage and hemolysis. The absorbance was measured at 405 nm at 0, 30, and 60 min, and then every 20 minutes for four hours. The time for 50 percent of maximal hemolysis (T50%), which expresses the radical scavenger activity of erythrocytes, was determined.

The physiologic T50% value determined in 52 healthy volunteers is 117 ± 12 min. Patients receiving these supplements have a higher value of T50% (143.2 ± 11.6 min at 30 d and 145.7 ± 10.5 min at 60 d) than the physiologic value (p<0.001).

These data suggest that vitamin C, vitamin E, and beta carotene stimulate the radical scavenger activity of erythrocyte membranes after 30 days.

To review the pharmacology, pharmacokinetic, dosing, adverse effects, and therapeutic uses of sotalol.

Articles were identified with an English-language literature computer search via Knowledge Finder, using the term sotalol, and with an extensive search of bibliographies of identified articles.

Relevant or representative animal studies, human trials, and case reports were selected for evaluation.

The literature was assessed for quality, methodology, and outcome information.

Sotalol is a racemic compound with Class II (beta-blocking properties) and Class III (prolonged action potential) antiarrhythmic activity. It has been suggested that the plasma concentration associated with QTc prolongation (a measure of the Class III action) is much greater than that associated with beta-blockade. Therefore, sotalol is categorized as a Class III antiarrhythmic agent. The l-isomer is responsible for the beta-blocking activity, whereas both isomers have Class III properties. After oral dosing in fasting patients with normal renal function, sotalol is >90 percent absorbed, achieves peak serum concentrations in 2–4 h, is excreted unchanged 80–90 percent in the urine, has a volume of distribution of 1–2L/kg, and has an elimination half-life of about 12 h. Sotalol is effective in patients with life-threatening ventricular arrhythmias that have been refractory to other conventional antiarrhythmic drugs. In general, sotalol appears to be well tolerated, with many of its adverse effects caused by beta-blocking activity. As with other antiarrhythmic agents, the possibility of proarrhythmia (frequently torsade de pointes) exists.

Racemic sotalol is an effective Class III antiarrhythmic agent approved by the Food and Drug Administration for the treatment of documented life-threatening ventricular arrhythmias. Investigations continue with racemic sotalol in the management of supraventricular arrhythmias. Trials with the d-isomer are also ongoing.

To discuss the chemistry, pharmacokinetics, spectrum of activity, clinical trials, adverse effects, drug interactions, and dosage guidelines of cefpodoxime proxetil.

Literature was identified through a MEDLINE search from 1988 to the present and from review of bibliographies in that literature.

Data were limited to comparative trials published in the English literature. Although many studies were conducted in Japan, the results often were available only in Japanese or partly in English. As these studies could not be completely evaluated, they are not included in this review.

Cefpodoxime exhibits good activity against many gram-positive and gram-negative organisms. In clinical trials, cefpodoxime was similar in both clinical and bacteriologic efficacy to amoxicillin, cefaclor, amoxicillin/clavulanate, and penicillin in the treatment of respiratory and urinary tract infections. It also appeared effective in the treatment of skin and soft tissue infections, although no comparative trials have been performed. Cefpodoxime is well tolerated by children and is effective in the treatment of otitis media and pharyngitis. It has a similar adverse effect profile to that of other penicillins and cephalosporins, with gastrointestinal effects being most common.

Cefpodoxime demonstrates good in vitro activity against pathogens frequently associated with respiratory tract, urinary tract, and skin and tissue infections. It has not demonstrated greater efficacy than the other antibiotics to which it has been compared. The available published clinical trials are fraught with methodologic, statistical, and evaluative flaws. Thus, further trials comparing cefpodoxime with established treatments, as well as the newer cephalosporins, are needed before its place in therapy can be established.

To report the clinical presentation and response to antimicrobial therapy of presumed bacillary angiomatosis in an AIDS patient.

Single case report.

A 1058-bed, university teaching hospital.

28-year-old HIV-positive man (T₄ lymphocyte count <3/mm³), who was diagnosed with AIDS in 1984.

The skin lesions responded promptly to treatment with doxycycline and erythromycin.

Bacillary angiomatosis is an infection that occurs with endstage AIDS. Skin lesions have recognizable characteristics and respond promptly to appropriate antibiotic therapy.

To review the literature on the physiologic changes created by neonatal patent ductus arteriosus (PDA) and the potential impact on drug disposition in these infants.

An Index Medicus and bibliographic search of the English-language literature pertaining to neonatal PDA and drug usage in newborns.

PDA in premature infants is associated with a variety of physiologic changes that could alter drug disposition. Perfusion of drug-elimination organs (i.e., liver and kidney) may be diminished, resulting in decreased drug elimination. Further, the general fluid overload state associated with PDA may result in larger volumes of distribution (V_d), and dilutional effects for many drugs. Drug absorption, V_d, tissue penetration, and clearance may be affected by the physiologic changes incurred by a PDA. Although the pharmacokinetics of several categories of therapeutic agents may be affected by a PDA, disposition changes with the aminoglycosides and indomethacin have been the best documented. The most reliable pharmacokinetic change appears to be related to drug V_d. The interpretation of many of these studies is confounded by a potential drug interaction with the concurrent administration of indomethacin for PDA closure.

Close therapeutic drug monitoring is indicated in newborns with PDAs as abrupt changes in drug disposition can occur with PDA closure. PDA-induced changes in specific pharmacokinetic parameters of agents such as the aminoglycosides, indomethacin, and perhaps vancomycin may prove to be a valuable diagnostic adjunct for the identification of babies with undiagnosed PDA. More research into this pharmacophysiologic aspect of pharmacokinetics is warranted.

To critically review available data on the effective lower end of the phenytoin therapeutic range for the treatment of seizure disorders.

Relevant articles were identified from an English-language search of MEDLINE 1982-1992. Additional references were found in bibliographies of these articles.

We reviewed articles that included data on serum phenytoin concentrations (SPCs) and seizure control. Data on concurrent anticonvulsants, seizure diagnosis, and seizure severity were extracted when available.

The original study defining the phenytoin therapeutic range as 10–20 mg/L is analyzed; it was based on a small, homogeneous sample that cannot be generalized to a more diverse epileptic population. Many studies report patients obtaining seizure control with SPCs below 10 mg/L. Studies including a range of seizure diagnoses and severity have a larger variability in effective SPCs; however, effective SPCs are reproducible.

The therapeutic range of phenytoin is defined on an individual basis. Some patients, especially those with infrequent, primary tonic-clonic seizures, may be controlled with phenytoin concentrations below the recognized reference range of 10–20 mg/L.

To develop a categorization scheme for grouping various nonsteroidal antiinflammatory drugs (NSAIDs) by relative safety; to develop a method to quantify the appropriateness of the initial and subsequent choices of NSAID therapy; to assess whether NSAID prescribing was consistent with the developed criteria; to examine the cost of inappropriate, acute NSAID use as defined by the established criteria.

Retrospective drug utilization review focusing on NSAIDs.

Members aged age⩾18 years of a 40 000-person southeastern Michigan health maintenance organization

(1) Appropriateness of therapy using a four-level safety classification system for the NSAIDs developed by a consensus process; criteria based on safety under the assumption that any particular NSAID is equally likely to be effective when dosed appropriately; (2) evaluation of progression of NSAID therapy using the NSAID Therapy Progression Formula.

For acute patients, almost half of the prescriptions were for ibuprofen and 33 percent were for naproxen. Ibuprofen usage accounted for 16 percent of total NSAID cost and naproxen agents accounted for over 50 percent of that cost. Potential cost savings of approximately $82 000 probably would have occurred had a 50 percent interchange rate for ibuprofen been acceptable. For chronic patients, 85 percent were treated with one or two NSAIDs; treatments were of reasonable high quality when compared by safety profiles. There was low use of ibuprofen in patients who only received one NSAID.

NSAID usage assessment in a large population was achieved by developing a classification and scoring system based on NSAID safety; in this population, prescribing patterns were generally consistent with established criteria; however, when considering cost, improvement in initial NSAID selection for acute patients was possible.