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Biomedical subjects

K A Rodvold

Publications and source records attributed to K A Rodvold.

At least 73 records · Page 4Linked to original sources
PubMed1989

Individualizing vancomycin dosage regimens: one- versus two-compartment Bayesian models.

The absolute and relative predictive performances of one- and two-compartment Bayesian forecasting models were evaluated and compared. Initial population parameters were derived from 25 adult patients with stable renal function and who were being treated for presumed or documented gram-positive infections. The performance of each model was compared using these population parameters with and without steady-state or non-steady-state feedback concentrations to predict future peak and trough concentrations in an additional 20 patients. Both models tended to underpredict vancomycin peak and trough concentrations obtained at steady state. The use of a two-compartment model resulted in statistically less bias and more precise predictions of vancomycin peak concentrations when either population parameters or non-steady-state concentrations were used for future predictions. No difference in model performance was observed when steady-state concentrations were used to predict future steady-state concentrations. The results of this evaluation demonstrate that the two-compartment Bayesian model is less biased and more precise in determining future vancomycin serum concentrations given only population parameters or non-steady-state feedback information. No difference in model performance could be discerned when steady-state concentrations were used as feedback information.

Adolescent↗
PubMed1988

Therapeutic update on glycopeptide and lipopeptide antibiotics.

Glycopeptide antibiotics in the form of vancomycin have been available for almost 30 years. In the past, vancomycin usually was reserved as an alternative agent to treat staphylococcal and streptococcal infection in patients with a penicillin allergy or hemodialysis shunt infection. With the increasing frequency of both methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, now it is often used as a first-line agent. Over a 10-year period, vancomycin sales have increased by almost $1 hundred million. Several new glycopeptide and lipopeptide antibiotics are in various stages of evaluation. While vancomycin resistance to date is a rare phenomenon, these drugs represent a potentially more potent and safer antibiotic alternative to vancomycin. Teicoplanin and daptomycin are two of these investigational agents.

Bacterial Infections↗
PubMed1988

Evaluation of theophylline overdoses and toxicities.

Patients presenting with elevated theophylline concentrations and manifestations of toxicity may be categorized as being either overdose or iatrogenic toxic. In addition to severe cardiac and neurologic toxicities, such as arrhythmias and seizures, OD patients probably require monitoring for manifestation of gastrointestinal hemorrhage, electrolyte abnormalities, and hypotension. The possibility of a delayed peak theophylline concentration after sustained release product ingestion must be considered. Patients with initial serum concentrations of less than 60 mg/L may receive a single dose of oral activated charcoal and have repeat concentrations drawn to ensure the avoidance of continued absorption. The presence of a serum concentration exceeding 60 mg/L in OD patients warrants initiation of elimination-enhancing modalities. Oral activated charcoal is the fastest and most readily available. Multiple-dose oral activated charcoal should be given until serum theophylline concentrations of 60 mg/L or less are reached. Cardiac monitoring and seizure precautions are recommended. Admission to the intensive care unit should be considered when serum concentrations do not decline after several hours of charcoal therapy or when seizures and severe cardiovascular manifestations occur. Patients having initial concentrations exceeding 100 mg/L and/or rapidly rising concentrations 100 mg/L over baseline values should be considered as candidates for CHP or RHP if available. If both CHP and RHP are unavailable or will be excessively delayed, HD is a reasonable alternative. Patients on chronic theophylline therapy (IA patients) presenting with symptoms of toxicity must be evaluated carefully. If serum concentrations are less than 20 mg/L, short-term observation or a reduction in dose should be sufficient. Patients with concentrations between 20 and 60 mg/L should be candidates for seizure precautions and cardiac monitoring. Oral activated charcoal may be started and continued until levels are below 20 mg/mL. Patients with concentrations in excess of 60 mg/L require intensive monitoring (including seizure precautions and cardiac monitoring) as well as initiation of MOAC or CHP/RHP as situation, availability, and patient tolerance dictate. Again, HD may be a reasonable alternative if the others are unavailable or contraindicated.

Adolescent↗
PubMed1988

Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition.

The effect of cardiopulmonary bypass (CPB) on the disposition of vancomycin (15 mg/kg) and of netilmicin (3 mg/kg) was studied in 10 adults. The concentration-time profile of the drug in serum and renal clearance were characterized pre-CPB, during CPB, and post-CPB. Vancomycin and netilmicin exhibited initial decreases in mean concentrations in serum of 4.0 mg/liter (16.8%) and 2.2 mg/liter (29.1%), respectively, upon initiation of CPB. Netilmicin concentrations in serum rebounded to a mean of 0.6 mg/liter (15.4%) within 90 min on CPB and then continuously decreased. Vancomycin concentrations in serum demonstrated a rebound increase of 2.3 mg/liter (23.5%) at the end of CPB when the aorta was unclamped. Mean renal clearance throughout CPB was decreased for vancomycin (58.4 to 43.4 ml/min per m2) and netilmicin (53.4 to 31.5 ml/min per m2). The rebound in vancomycin concentration in serum strongly correlated with the length of time between unclamping the aorta and coming off CPB (r = 0.94), as well as with the increase in temperature upon rewarming (r = 0.92).

Adult↗
PubMed1988

Vancomycin pharmacokinetics in patients with various degrees of renal function.

The influence of age, protein binding, and renal function on the pharmacokinetics of intravenous vancomycin was evaluated in 37 adult patients with various degrees of renal function. Patients were categorized into three groups based on measured creatinine clearance (CLCR): groups 1, 2, and 3 had 24-h CLCRs of greater than 70, 40 to 70, and 10 to 39 ml/min per 1.73 m2, respectively. After 1 h of intravenous infusion, concentrations of vancomycin in serum declined in a biexponential manner in all patients. Diminished renal function in groups 2 and 3 was accompanied by a lower total body vancomycin clearance (CL) (52.6 and 31.3, respectively, versus 98.4 ml/min per 1.73 m2) and a lower renal vancomycin clearance (CLR) (48.2 and 19.8, respectively, versus 88.0 ml/min per 1.73 m2) than in group 1. No significant differences in apparent distribution volume of the central compartment or apparent distribution volume at steady state were observed. Mean serum protein binding of vancomycin was 30% and was not significantly affected by renal function. Stepwise multiple linear regression analysis revealed that CLCR was the strongest predictor of vancomycin CL (r = 0.77, P less than 0.001) and vancomycin CLR (r = 0.87, P less than 0.001). Age did not significantly improve these correlations once CLCR was included. The relationship of vancomycin CL and CLCR was utilized to develop the following equation to dose vancomycin in the majority of renally impaired patients: dose (milligrams per kilogram per 24 h) = 0.227CLCR + 5.67, where CLCR is standardized to milliliters per minute per 70 kg. The practical dosing intervals that the calculated dose can be divided into and administered include 8, 12, 24, and 48 h based on the CLCR of the patient.

Adult↗
PubMed1988

Doxorubicin clearance in the obese.

A study was carried out to examine the effect, if any, of obesity on doxorubicin pharmacokinetics. Body weight was found to be significantly related to doxorubicin clearance (r = -.75; P less than .001) and elimination half-life (r = .62; P = .003). Thus, the contribution of obesity on pharmacokinetics of antineoplastic agents should be taken into consideration in the analysis of clinical data with respect to toxicity and tumor response. Twenty-one patients were studied with their first course of doxorubicin (50 to 70 mg/m2) administered as a 60-minute intravenous (IV) infusion. Patients were divided into three groups on the basis of percentage of ideal body weight (IBW): normal (less than 115% IBW), mildly obese (115% to 130% IBW), and obese (greater than 130% IBW). Blood samples were collected up to 48 hours after the infusion and analyzed for doxorubicin and its metabolite, doxorubicinol, by high performance liquid chromatography. Doxorubicin area under the curve (AUC) was greater in obese than in normal patients (2,209 v 1,190 ng h/mL; P less than .05), yielding correspondingly reduced systemic clearance of the agent in obese patients (891 v 1,569 mL/min; P less than .001). The mean elimination half-life (T1/2) was 20.4 hours in the obese patients and 13.0 hours in the normal patients. The apparent volume of distribution (Vss) was not significantly different among the three groups of patients, indicating that the prolonged T1/2 in the obese patients is due to the reduction in clearance. The AUC and T1/2 of doxorubicinol were similar among all patient groups.

Body Weight↗
PubMed1988

Teicoplanin: an investigational glycopeptide antibiotic.

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, adverse effects, and clinical uses of teicoplanin are reviewed. Teicoplanin, a novel glycopeptide that is similar to vancomycin, was isolated in the mid-1970s. A fermentation product of Actinoplanes teicomyceticus, teicoplanin is a structurally complex compound made up of six fatty-acid components attached to a common aglycone. Teicoplanin's mechanism of action, like that of vancomycin, is inhibition of cell-wall biosynthesis. In vitro activity is comparable to that of vancomycin and includes staphylococci, streptococci, corynebacterium, listeria, and anaerobic cocci. Resistance to teicoplanin has been reported with coagulase-negative staphylococci. Teicoplanin is 50 to 100 times more lipophilic than vancomycin. Teicoplanin is poorly absorbed after oral administration but is 90% bioavailable when administered intramuscularly. The drug distributes widely into body tissue and is eliminated primarily renally. Optimal dosing regimens and therapeutic serum drug concentrations have not been well established. Reported adverse effects have included irreversible ototoxicity, allergic reactions with maculopapular rash and eosinophilia, pain at intramuscular injection site, and elevation of aminotransferases. Initial clinical trials have yielded conflicting results in gram-positive bacteremia, endocarditis, osteomyelitis, and soft-tissue infections. Teicoplanin has shown promise in surgical and dental prophylaxis. Comparative trials with vancomycin and other antimicrobial agents must be completed before teicoplanin's role as a therapeutic agent in the treatment of systemic gram-positive infections is defined.

Animals↗
PubMed1988

Therapeutic considerations for infections caused by Staphylococcus epidermidis.

Most institutions are experiencing increased numbers of methicillin-resistant S. epidermidis infections. Currently, vancomycin is the only antibiotic that provides reliable bactericidal activity against this microorganism, including methicillin-resistant strains. Vancomycin is the treatment of choice for infections caused by methicillin-resistant staphylococci and for serious gram-positive infections in penicillin-allergic patients. With the emergence of more numerous and more serious gram-positive infections, this agent either alone or in combination with other antibiotics will clearly assume greater importance in the management of gram-positive infections, independent of host allergy or bacterial resistance. It is assuming a pivotal role in the treatment of gram-positive infections of central nervous system or dialysis shunts, endocarditis, meningitis, and septicemia. Except in patients with confirmed allergy to a beta-lactam antibiotic, vancomycin is not indicated for routine surgical prophylaxis. The current upsurge in methicillin-resistant staphylococcal infections as a complication of implant surgery may necessitate its use as a prophylactic agent, however.

Adult↗
PubMed1988

Stability of nizatidine in commonly used intravenous fluids and containers.

The stability of nizatidine in commonly used i.v. fluids stored in glass and plastic containers was studied. Stock solutions of nizatidine 0.75, 1.5, and 3.0 mg/mL in 15 i.v. fluids were prepared using nizatidine injection 25 mg/mL. Six 50-mL aliquots of each solution were transferred to separate glass infusion bottles and stored at room temperature or under refrigeration. Twenty-one 40-mL aliquots of additional stock solutions of nizatidine 0.75 and 3.0 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were transferred to polyvinyl chloride (PVC) bags and stored at room or refrigerated temperature; some of these solutions were frozen, thawed, and refrigerated before analysis. Samples of each admixture were analyzed after 0.5, 1, 2, 3, and 7 days of storage for nizatidine concentration using a stability-indicating high-performance liquid chromatographic assay and also for visible changes and pH. The concentration of nizatidine in each admixture remained within 92%-106% of actual initial storage concentration throughout the study period, with the exception of nizatidine 3.0 mg/mL in 8.5% amino acid injection. The stability of nizatidine in admixtures stored in polyvinyl chloride bags was similar to that of admixtures stored in glass bottles. In the i.v. fluids, concentrations, and containers studied, nizatidine admixtures are stable for at least 7 days at either room or refrigerated temperature and 30 days when stored frozen in polyvinyl chloride bags. Admixtures of nizatidine 3.0 mg/mL in 8.5% amino acid injection should not be stored at room temperature for longer than four days.

Chromatography, High Pressure Liquid↗
PubMed1987

Interaction of steady-state procainamide with H2-receptor antagonists cimetidine and ranitidine.

This study was designed to compare the effects of equivalent therapeutic doses of two H2 antagonists, cimetidine and ranitidine, on steady-state procainamide pharmacokinetics. Six healthy men were given 500 mg sustained-release procainamide every 6 h, for a total of 13 doses, on three occasions. Subjects were randomly assigned to three treatments by a Latin-square design: cimetidine 1,200 mg/day, ranitidine 300 mg/day, and no H2-receptor antagonist (control) for 4 days. Cimetidine significantly increased the procainamide area under the serum concentration-time curve by 43%, decreased renal clearance by 36%, and decreased the ratio of systemic clearance of procainamide to bioavailability by 28%. Ranitidine did not significantly alter procainamide steady-state pharmacokinetics.

Acecainide↗
PubMed1987

The pharmacokinetics of naloxone in the premature newborn.

We examined the pharmacokinetic properties of naloxone in a group of premature infants infused with an intravenous bolus of the drug. Ten infants with a mean birth weight of 1,328 +/- 402 g and a gestational age of 29.4 +/- 2.8 weeks were studied at an age of 4.5 +/- 3.2 days of life. Following administration of 0.4 mg/kg of naloxone, we obtained blood samples at specific time intervals, and stored the serum for later analysis by a radioimmunoassay method. Calculations from the serum concentration versus time relationship resulted in an elimination rate constant of 0.75 +/- 0.39/h, a half-life of 70.5 +/- 35.2 min, a systemic clearance of 39.13 +/- 14.53 ml/min/kg, and an apparent volume of distribution of 3.52 +/- 1.20 liters/kg.

Humans↗
PubMed1987

Recognition and importance of Staphylococcus epidermidis infections.

The bacteriology, epidemiology, pathogenesis, clinical features, antimicrobial susceptibility, and therapy of Staphylococcus epidermidis infections are reviewed. Staph. epidermidis is often regarded as a culture contaminant, but its importance as a pathogen has been recognized in recent years. Except for native-valve endocarditis, most Staph. epidermidis infections are hospital-acquired. Staph. epidermidis is a common cause of infections involving indwelling foreign devices, surgical wound infections, and bacteremia in immunocompromised patients. The occult nature of these infections and low virulence of the organism make diagnosis and treatment difficult. Staph. epidermidis isolates from nosocomial infections frequently are resistant to methicillin; however, resistant isolates often appear to be susceptible to methicillin unless reliable methods of susceptibility testing are used. Cross-resistance between methicillin and cephalosporins occurs in vitro. Virtually all Staph. epidermidis isolates are susceptible in vitro to vancomycin and rifampin. Penicillin G, semisynthetic penicillinase-resistant penicillins, and cephalosporins are effective for the treatment of methicillin-sensitive Staph. epidermidis infections. Vancomycin is the drug of choice for infections caused by methicillin-resistant organisms. Vancomycin, combined with rifampin or gentamicin, or both, is recommended for therapy of serious infections caused by methicillin-resistant strains. Staph. epidermidis is an important pathogen in immunocompromised patients and patients who develop nosocomial bacteremia; treatment usually consists of antimicrobial therapy and removal of indwelling catheters or devices.

Catheterization↗
PubMed1986

The pharmacodynamic and pharmacokinetic differences of the D- and L-isomers of verapamil: implications in the treatment of paroxysmal supraventricular tachycardia.

There is increasing interest in defining the pharmacodynamic and pharmacokinetic characteristics of drugs that are marketed as racemic mixtures. Verapamil is one such drug that is commercially available as a mixture of D- and L-isomers. The L-isomer of verapamil has a greater-negative inotropic, negative chronotropic, and negative dromotropic potency than the D-isomer. The values for fraction unbound in serum, distribution volume, and systemic clearance are substantially greater for the L-isomer after intravenous dosing. After oral dosing, the D-isomer achieves peak plasma concentrations five times greater than the L-isomer. The pharmacodynamic and pharmacokinetic characteristics of each isomer are reviewed. The differences in the concentrations of the D- and L-isomers after oral vs intravenous dosing may contribute to the relatively lower efficacy of orally administered verapamil in the treatment of PSVT.

Administration, Oral↗
PubMed1986

Accuracy of 11 methods for predicting theophylline dose.

Eleven methods for pharmacokinetic determination of theophylline dose were compared, based on the ability of each method to predict theophylline serum concentration and clearance for adults with asthma. Predictions by each method were compared with actual serum theophylline concentrations before and after an aminophylline loading dose was administered to treat bronchospasm in 22 patients. Follow-up serum theophylline concentrations were obtained after maintenance therapy with i.v. aminophylline in 6 patients and an oral sustained-release theophylline product (Theo-Dur, Key) in 16 patients; maintenance doses administered to the patients were calculated by the method of Chiou et al. Two variations of the method of Chiou et al., seven Bayesian methods using one or more measured serum theophylline concentrations, FDA's standardized clearance estimate, and a population-based clearance-estimation method were compared. A one-compartment, open model with first-order elimination was assumed for all calculations. All 11 methods predicted steady-state concentration with minimal bias and good precision. The Chiou and Bayesian methods performed similarly, with the highest precision found for the Bayesian method that incorporated four measured concentrations. The population-based method had the highest correlation coefficient and the lowest mean error for predicting steady-state concentration. Decreasing the number of measured concentrations had a minimal effect on the various Bayesian methods. All methods evaluated are sufficiently accurate for clinical application in patients with stable, uncomplicated asthma.

Acute Disease↗
PubMed1984

Heparin-induced thrombocytopenia in patients with cerebrovascular ischemic disease.

We studied 137 patients who were treated with heparin for cerebral infarction (73), partially reversible ischemic neurologic deficit (22), or transient ischemic attack (42). Platelet counts were performed before therapy, twice weekly, and at cessation of therapy. Platelets decreased in 118 patients (86%). In 21 (15.3%), platelets dropped greater than or equal to 40%; 9 of 14 new ischemic events and three of six deaths occurred in this group of patients. Because there was a significant association between poor outcome and platelet drop greater than or equal to 40% (p less than 0.001), we believe that platelets should be monitored frequently when patients are treated with heparin for ischemic cerebrovascular disease.

Adult↗
PubMed1983

Heparin-associated thrombocytopenia: a prospective evaluation of 211 patients.

Two hundred eleven consecutive patients treated for acute thromboembolic disease were evaluated prospectively for the incidence of thrombocytopenia while receiving heparin treatment. One hundred patients received beef lung heparin and 111 patients received porcine intestinal mucosal heparin. All patients received a minimum of 4 consecutive days of continuous intravenous heparin, and platelet counts were determined prior to, at least twice weekly, and at the cessation of heparin therapy. Heparin-associated thrombocytopenia was defined as a decline from a normal platelet count (100,000-400,000/mm3) to less than 100,000/mm3 with a return to above 100,000/mm3 after the discontinuation of heparin. Heparin-associated thrombocytopenia developed in 11 patients (5.2% incidence). Ten of the thrombocytopenic patients had received beef lung heparin and one received porcine mucosal heparin. Chi-square analysis of these data was significant (p = 0.007). Plasma from seven of nine thrombocytopenic patients demonstrated a plasma factor compatible with a heparin-sensitive antiplatelet antibody. Heparin-associated thrombocytopenia appeared on days 2 to 10 of therapy. Cessation of heparin resulted in remission of thrombocytopenia within 4 days in all patients. Serial quantitative platelet count determinations are indicated in all patients receiving therapeutic heparinization for the early recognition and resolution of heparin-associated thrombocytopenia.

Adolescent↗