Patient-controlled analgesia Reports
`
`convenience excellent or good. Of the 103 nurses,
`80 opined that the PCA service saved them time,
`and several commented that a major advantage was
`that only one person, the clinical pharmacist, need(cid:173)
`ed to be contacted for any problem. Seventy-one
`patients rated the PCA method highly, and most
`indicated that they would prefer a hospital with
`PCA services should they require surgery in the
`future.
`
`Cone I us Ion
`
`Our comprehensive, pharmacy-based PCA ser(cid:173)
`vice offers patients better control of pain with less
`sedation, allows pharmacists to demonsJrate com-
`
`petence in nondistributive functions, increases the
`visibility of the pharmacy department to patients
`and the medical staff, and is a source of revenue.
`The service has been well accepted by patients,
`nurses, and physicians.
`
`asilverman HM, Bard MedSystems Division of C. R. Bard, Inc.
`Personal communication. 1986Nov11.
`
`References
`1. McKenna TR, Branigan TA, Sorocki AH. Pharmacist-initiat(cid:173)
`ed introduction of patient-controlled analgesia to a 400-bed
`community hospital. Am J Hosp Pharm.1989; 46:291-4.
`2. Walker WE, Coons C, Matte D et al. Hydromorphone and
`morphine stability in portable infusion pump cassettes and
`minibags. Can J Hosp Pharm. 1988; 41(4):177-82.
`
`Sorption of various drugs in polyvinyl chloride, glass,
`ard polyethylene-lined infusion containers
`HARRIE J. MARTENS, PIETER N. DE GOEDE, AND ARIE C. VAN LOENEN
`
`Abstract: The sorption of chloro(cid:173)
`quine sulfate, diazepam, isosorbide
`dinitrate, lorazepam, midazolam,
`nitroglycerin, promethazine hy(cid:173)
`drochloride, thiopental sodium,
`and warfarin sodium to three types
`of containers was studied.
`Appropriate amounts of the
`drugs were added to 500 mL of 0.9%
`sodium chloride injection in poly(cid:173)
`vinyl chloride (PVC) bags, glass
`bottles, and Clear-Flex bags com(cid:173)
`posed of a laminate of polyethyl(cid:173)
`ene, nylon, and polypropylene.
`The containers were stored in the
`dark at room temperature for 24
`hours. Samples were taken at vari(cid:173)
`ous intervals and assayed for drug
`concentration by high-perform(cid:173)
`ance liquid chromatography.
`There were no appreciable
`
`changes in pH after 24 hours, and
`all the admixtures remained clear
`and colorless. The potency of chlo(cid:173)
`roquine sulfate, lorazepam, mida(cid:173)
`zolam, promethazine hydrochlo(cid:173)
`ride, and thiopental sodium re(cid:173)
`mained unchanged in glass, PVC,
`and Clear-Flex containers. Diaze(cid:173)
`pam, isosorbide dinitrate, nitro(cid:173)
`glycerin, and warfarin sodium did
`not show any sorption to glass bot(cid:173)
`tles and Clear-Flex bags. In PVC
`bags, however, up to 55% of diaze(cid:173)
`pam, 23% of isosorbide dinitrate,
`51 % of nitroglycerin, and 24% of
`warfarin sodium was lost during
`the 24-hour study period.
`Diazepam, isosorbide dinitrate,
`nitroglycerin, and warfarin sodium
`in 0.9% sodium chloride injection
`showed a loss of potency when
`
`stored in PVC containers for 24
`hours at room temperature, but
`none of the drugs studied lost po(cid:173)
`tency when stored in glass bottles
`and Clear-Flex bags.
`
`Index terms: Additives; Anesthet(cid:173)
`ics; Anticoagulants; Antihistamines;
`Antimalarial agents; Anxiolytics, sed(cid:173)
`atives and hypnotics; Chloroquine
`sulfate; Containers; Diazepam; Glass;
`Hydrogen ion concentration; In(cid:173)
`compatibilities; Injections; Isosorbide
`dinitrate; Lorazepam; Midazolam;
`Nitroglycerin; Polyethylene; Poly(cid:173)
`vinyl chloride; Potency; Prometha(cid:173)
`zine hydrochloride; Sodium chlo(cid:173)
`ride; Sorption; Stability; Storage;
`Thiopental sodium; Vasodilating
`agents; Warfarin sodium
`Am J Hosp Pharm. 1990; 47:369-73
`
`Certain drugs, including insulin, nitroglycerin,
`isosorbide dinitrate, chloroquine, clomethiazole,
`diazepam and other benzodiazepines, warfarin so(cid:173)
`dium, thiopental sodium, and some phenothi(cid:173)
`azines, show losses from aqueous solutions stored
`in infusion containers.1- 4 Such losses may result in
`reduced delivery of drugs to patients. Fortunately,
`drug loss from infusion solutions is likely to
`
`present a clinical hazard in only a few cases. Gener(cid:173)
`ally, these losses have been attributed to an interac(cid:173)
`tion between the drug and the infusion container.
`Polyvinyl chloride (PVC) seems to be the main
`offender in this interaction.2
`Documentation of the compatibility of drugs
`with infusion containers is limited. The main
`physicochemical determinants controlling sorp-
`
`HARRIE J. MARTENS, PHARM.D., is Staff Clinical Pharmacist,
`and PIETER N. DE GOEDE is Head Technician, Laboratory of
`Drug Analysis and Toxicology, Department of Pharmacy, Free
`University Hospital, Amsterdam, The Netherlands. ARIE C.
`v AN LOENEN, PHARM.D., is Head, Department of Pharmacy,
`Free University Hospital.
`
`Address reprint requests to Dr. Mai:tens at Free University
`Hospital, Department of Pharmacy, De Boelelaan 1117, 1081
`HV, Amsterdam, The Netherlands.
`
`Copyright© 1990, American Society of Hospital Pharmacists,
`Inc. All rights reserved. 0002-9289/90/0201-0369$01.25.
`
`Vol 47 Feb 1990 American Journal of Hospital Pharmacy 369
`
`Hospira, Exh. 2020, p. 1
`
`

`
`Reports Sorption of drugs to containers
`
`tion of a drug appear to be.the lipophilic properties
`of the drug, storage time and temperature, drug
`concentration, the extent of ionization (which is
`pH dependent), and the surface area-to-volume ra(cid:173)
`tio of the container. 1
`With the recent introduction in Europe of a
`three-layer laminate bag (Clear-Flex) that is com(cid:173)
`posed of polypropylene, nylon, and polyethylene
`and has low permeability to oxygen and water va(cid:173)
`por, 5 it is important to know if drug sorption to this
`new material is less than with PVC. A similar bag is
`also available in the United States.3 Polyethylene,
`the inner material, does not seem to show a sub(cid:173)
`stantial sorptive interaction with the drugs men(cid:173)
`tioned above.3,4 The container material does not
`contain plasticizers and has an envfronmental ad(cid:173)
`vantage over PVC because it does not produce hy(cid:173)
`drochloric acid when it is burned.
`The purpose of our study was to compare the
`sorptive profiles of chloroquine sulfate, diazepam,
`isosorbide dinitrate, lorazepam, midazolam hydro(cid:173)
`chloride, nitroglycerin, promethazine hydrochlo(cid:173)
`ride, thiopental sodium, and warfarin sodium in
`PVC, glass, and Clear-Flex containers.
`
`Methods
`
`Admixture Preparation. Drugs were added in
`appropriate amounts to 500 mL of 0.9% sodium
`chloride injection in PVC bags,a Clear-Flex bags,b
`and clear glass bottlesc to obtain test solutions,
`which contained 12-hour dosages used in clinical
`practice. Chloroquine sulfate test solution was pre(cid:173)
`pared by adding 5 mL of the contents of chloro(cid:173)
`quine sulfate 50-mg/mL ampulsd in a plastic dis(cid:173)
`posable syringe to the contents of the containers;
`diazepam by adding 4 mL of 5-mg I mL am puls, e
`isosorbide dinitrate by adding 50 mL of 1-mg/mL
`ampuls/ lorazepam by adding 5 mL of 4-mg/mL
`ampuls,g midazolam hydrochloride by adding 4
`mL of 5-mg/mL ampuls,h nitroglycerin by adding
`10 mL of 5-mg/mL ampuls,i promethazine hydro(cid:173)
`chloride by adding 2 mL of 25-mg/mL ampuls,i
`and warfarin sodium by adding 2.5 mL of 2-mg / mL
`ampuls.k Thiopental sodium test solution was pre(cid:173)
`pared by reconstituting a 0 .5-g vial 1 of drug with 20
`mL of water for injection. Approximately 40 mL of
`this solution was added to the Clear-Flex contain(cid:173)
`ers.
`Conditions and Sampling. Each type of solution
`was prepared in triplicate. The test solutions were
`stored at room temperature (21 °C) for 24 hours
`and were protected from light. To comply with
`standard sterility guidelines involving the time of
`expiration of intravenous admixtures, a 24-hour
`study period was chosen. The 24-hour period rep(cid:173)
`resents the maximum storage time of i.v. admix(cid:173)
`tures in our hospital. The test solutions were visu(cid:173)
`ally inspected for color and clarity immediately
`after mixing and at 1, 2, 4, 6, and 24 hours. At each
`
`interval, duplicate samples were taken with 1-mL
`plastic disposable syringesm and were assayed by
`high-performance liquid chromatography (HPLC)
`to determine drug concentrations. For nitroglycer(cid:173)
`in and isosorbide dinitrate, additional samples
`were taken at 15 and 30 minutes. Solution pH was
`measured with a Consort P914 pH metern immedi(cid:173)
`ately after mixing and at 24 hours.
`HPLC Analysis. Drug concentrations were mea(cid:173)
`sured by HPLC at 21 ± 1 °C. A model 45 solvent(cid:173)
`delivery pump,0 a U6K injector0 with a fixed 10-µL
`or 50-µL loop, a model 440 dual-wavelength detec(cid:173)
`tor, 0 and a Shimadzu Chromatopac C-R3A integra(cid:173)
`torP were used. A 10-µL portion (for warfarin, 50
`µL) of each sample was injected into the HPLC
`system. The use of a fixed loop obviated the need
`for internal standardization. Separations were
`achieved for chloroquine on a Lichrosorb 10 RP 8
`stainless steel columnP (4.6 mm X 25 cm) with a
`mobile phase of water-tetrahydrofuran-triethyla(cid:173)
`mine (96:4:0.75) adjusted to a final pH of 2.3 with 2
`M nitric acid (flow rate, 2 mL/min); for diazepam,
`lorazepam, and thiopental on a Lichrosorb 10 RP 8
`column with a mobile phase of water-methanol(cid:173)
`tetrahydrofuran (50:50:5) (3 mL/min); for isosor(cid:173)
`bide dinitrate and nitroglycerin on a Lichrosorb 10
`RP 8 column with a mobile phase of water-metha(cid:173)
`nol (50:50) (2 mL/min); for midazolam and pro(cid:173)
`methazine on a µ-Bondapak C1s stainless steel col(cid:173)
`umn0 (3.9 mm X 30 cm) with a mobile phase of
`acetonitrile-0.1 M dibasic potassium phosphate
`buffer (33:67) adjusted to a final pH of 4.4 with
`phosphoric acid (1.7 mL/min); and for warfarin
`sodium on a Novapak C18 Radial-Pak cartridge0 (8
`mm X 10 cm) with a mobile phase of 1.5% acetic
`acid-acetonitrile (69:31) adjusted to a final pH of
`4.2 with 1 M sodium hydroxide (4.2 mL/min). De(cid:173)
`tection took place at a wavelength of 254 nm except
`for isosorbide dinitrate and nitroglycerin, which
`were detected at 214 nm.
`All other chemicals and reagents used were of
`analytical grade.q Drug concentrations were deter(cid:173)
`mined by comparing peak heights with those of
`standard solutions prepared by diluting one fifth
`of the volume of the drug productsa-f used in ad(cid:173)
`mixture preparation with 0.9% sodium chloride in(cid:173)
`jection to a final volume of 100 mL.
`Precision and retention time data for each drug
`are listed in Table 1.
`
`Resuns and Discussion
`
`Chloroquine sulfate, lorazepam, midazolam,
`promethazine hydrochloride, and thiopental sodi(cid:173)
`um in 0.9% sodium chloride injection did not de(cid:173)
`crease in concentration when stored in glass, PVC,
`and Clear-Flex containers (Table 2). There were no
`appreciable changes in pH (Table 3), and all admix(cid:173)
`tures remained clear and colorless after 24 hours.
`The concentration of diazepam declined rapidly
`
`370 American Journal of Hospital Pharmacy Vol 47 Feb 1990
`
`Hospira, Exh. 2020, p. 2
`
`

`
`Sorption of drugs to containers Reports
`
`Table 1.
`Retention Time and Precision Data for the High-Performance Liquid Chromatographic Method Used
`
`Drug
`
`Chloroquine sulfate
`Diazepam
`lsosorbide dinitrate
`Lorazepam
`Midazolam hydrochloride
`Nitroglycerin
`Promethazine hydrochloride
`Thiopental sodium
`Warfarin sodium
`
`Retention
`Time(min)
`
`5.2
`10.0
`3.8
`8.0
`5.1
`5.8
`5.5
`11.2
`14.0
`
`Linearity
`(µg/mL)
`
`125-500
`20-40
`25-100
`20-40
`10-40
`25-100
`25-100
`100-2000
`2.5-10
`
`Correlation
`Coefficient
`
`Coefficient of
`Variation ( % )
`
`1.000
`0.9997
`1.000
`0.9997
`1.000
`1.000
`1.000
`0.9999
`0.9995
`
`0.3(n 9)
`0.8 (n= 9)
`2.0 (n= 6)
`0.6(n=9)
`2.5 (n = 6)
`2.0 (n= 6)
`1.5 (n = 6)
`0.8(n 9)
`3.6 (n 9)
`
`Table 2.
`Sorptlon of Drug Admixtures In 0.9% Sodium Chlorlde Injection In Different Containers Stored at 21 °C In Darkness•
`
`Drug and
`Container
`
`Actual Initial
`Concentration
`(µg/mL)
`
`15min
`
`30min
`
`1 hr
`
`% Remaining
`2 hr
`
`4 hr
`
`6 hr
`
`24 hr
`
`Chloroquine
`sulfate
`Glass bottle
`PVCb bag
`Clear-Flex bagc
`Diazepam
`Glass bottle
`PVC bag
`Clear-Flex bag
`lsosorbide
`di nitrate
`Glass bottle
`PVC bag
`Clear-Flex bag
`Lorazepam
`Glass bottle
`PVC bag
`Clear-Flex bag
`Midazolam
`Glass bottle
`PVC bag
`Clear-Flex bag
`Nitroglycerin
`Glass bottle
`PVC bag
`Clear-Flex bag
`Promethazine
`hydrochloride
`Glass bottle
`PVC bag
`Clear-Flex bag
`Thiopental
`sodium
`Glass bottle
`PVC bag
`Clear-Flex bag
`Warfarin
`sodium
`Glass bottle
`PVC bag
`Clear-Flex
`
`482 ± 8.8
`482 ± 6.1
`497 ±4.2
`
`38.6 ± 1.2
`37.3 ± 2.1
`39.1±0.6
`
`95.3 ± 2.1
`93.0 ± 4.1
`98.8 ± 1.5
`
`38.9 ± 2.2
`38.1 ±3.0
`39.4 ± 0.8
`
`36.4 ± 2.2
`36.1±4.2
`39.6 ± 1.1
`
`102 ± 3.9
`101±3.1
`106 ± 2.1
`
`95.2 ± 1.9
`90.4 ± 4.1
`96.3 ± 2.3
`
`1803 ± 32
`1746 ± 44
`1817 ± 29
`
`10.5 ± 0.4
`9.5 ± 0.7
`10.3 ± 0.5
`
`99.8 ± 0.2 100.5 ± 0.6
`99.9 ::i: 0.6 100.0 ± 0.5
`100.3 ± 0.4
`98.9 ± 0.8
`100.1±0.7 100.8 ± 0.8
`98.4 ± 1.1
`99.8 ± 1.2
`101.1±0.5 100.2 ± 1.3 100.0 ±0.9 99.2 ± 0.9
`99.0 ± 1.4
`
`99.7 ± 1.3 100.3 ± 1.6
`100.6 ± 0.3
`85.1±2.5
`77.3 ± 3.6
`95.5 ± 1.3
`99.6 ± 1.5 100.4 ± 1.1 101.0± 1.2
`
`99.8 ± 2.2
`66.9 ± 4.4
`99.5 ± 0.8
`
`99.1±2.8
`45.3 ± 2.5
`98.5 ± 0.7
`
`101.2 ± 1.8 100.0 ± 0.9 100.8± 0.7
`99.1±2.1 96.8 ± 1.9
`94.1±1.7
`99.1±1.3 99.5 ± 1.5
`98.1±1.5
`
`99.6 ± 1.2 100.3 ± 1.4
`99.7 ± 1.1 100.2 ± 1.5
`84.7 ± 1.8
`77.3 ± 2.6
`90.8 ± 2.2
`88.8 ± 2.8
`97.9 ± 1.9
`98.3 ± 0.9 101.2 ± 2.4
`98.5 ± 2.1
`
`101.3± 1.1 102.1 ± 2.1 100.2 ± 1.5
`99.1±0.9
`99.3 ± 0.8
`97.8 ± 1.0
`100.1 ± 0.6 99.3± 1.1
`98.5 ± 0.7
`
`99.6 ± 0.4
`98.8 ± 1.1
`99.1±0.9
`
`99.2 ± 0.6
`97.4 ± 1.3
`98.6 ± 1.7
`
`99.7 ± 0.6 100.5 ± 1.5 100.8 ± 1.2 102.1±2.1
`101.3 ± 0.8
`99.5 ± 1.3
`99.8 ± 1.3
`97.7 ± 1.8
`98.3 ± 1.9
`99.1±0.7
`100.7 ± 0.8 101.2 ± 1.2 100.1 ± 1.6 100.6 ± 1.9 102.0 ± 1.8
`
`100.2 ± 0.5 100.5 ± 0.7
`96.2 ±0.9 91.0 ± 2.2
`99.7 ± 1.2 100.3 ± 1.5
`
`99.3± 1.1
`89.5 ± 2.7
`99.0 ± 1.5
`
`99.1±0.6 100.5 ± 1.5 98.8± 1.1
`86.5 ± 3.8
`79.1±4.1
`67.8 ± 5.8
`95.1±2.1
`98.5 ± 1.3
`97.2 ± 1.9
`
`97.8 ± 1.3
`49.4 ± 6.2
`94.5 ± 2.6
`
`100.1±0.5 99.8 ± 0.6 101.0 ± 1.5 100.8 ± 1.0 100.5 ± 0.4
`98.1±1.7
`99.8 ± 1.2
`98.6 ± 1.3
`99.7 ± 0.6 100.2 ± 0.7
`100.3 ± 0.9 100.6 ± 1.1 100.1±0.8 99.9 ± 1.9 101.7 ± 2.0
`
`97.8 ± 1.5
`99.9 ± 1.6
`99.3 ± 1.4
`99.6 ± 1.4
`100.4±1.7 100.4 ± 1.9
`99.4 ± 1.5 100.1±1.6 100.2 ± 1.9
`
`97.8 ± 1.2
`98.9 ± 1.8
`99.2 ± 1.4
`
`98.1±1.8
`97.8 ± 2.1
`99.1±1.2
`
`101.3 ± 2.4 100.9 ± 2.6 102.0 ± 2.5 100.8 ± 3.2 100.1±3.2
`96.8 ± 1.3
`76.5 ± 0.7
`94.2 ± 1.8 89.1±1.2 87.9± 1.1
`100.4 ± 0.8
`97.2 ± 1.4
`98.8 ± 1.1
`98.2 ± 1.9
`99.2 ± 1.0
`
`a Values expressed as mean± S.D. for three determinations.
`PVC = polyvinyl chloride.
`Medital, Ede, The Netherlands, lot 86 K 17-4234.
`
`Vol 47 Feb 1990 American Journal of Hospital Pharmacy 371
`
`Hospira, Exh. 2020, p. 3
`
`

`
`Reports Sorption of drugs to containers
`
`Table 3.
`pH Values for Drug Admixtures In 0.9% Sodium Chloride Injection In Different Containers Stored at 21 °C In Darknessa
`
`Chloroquine sulfate
`Diazepam
`lsosorbide dinitrate
`Lorazepam
`Midazolam
`Nitroglycerin
`Promethazine hydrochloride
`Thiopental sodium
`Warfarin sodium
`
`Glass
`Bottle
`
`6.9 ± 0.10
`6.8 ± 0.05
`6.8 ±0.09
`6.3 ± 0.04
`6.3 ±0.05
`6.6 ±0.02
`6.3 ± 0.04
`9.1 ±0.02
`6.0 ± 0.02
`
`Initial ~H
`PVC
`
`Clear-Flexc
`
`6.8±0.06
`6.8± 0.03
`6.6± 0.04
`6.5 ±0.05
`5.9± 0.08
`6.4± 0.03
`5.9± 0.08
`9.1±0.05
`6.2 ±0.07
`
`6.8 ± 0.04
`6.6± 0.05
`6.6 ± 0.06
`6.2 ± 0.07
`6.5± 0.03
`6.4 ± 0.05
`6.5 ± 0.07
`9.1±0.08
`6.1±0.06
`
`Glass
`Bottle
`
`7.0 ± 0.05
`6.7 ± 0.07
`6.6 ±0.08
`6.5 ± 0.07
`6.5 ±0.06
`6.6 ± 0.02
`6.3 ± 0.03
`9.0 ± 0.08
`6.1±0.05
`
`~H after 24 hr
`PVC
`
`Clear-Flex
`
`6.8 ± 0.06
`6.8 ± 0.03
`6.8 ± 0.05
`6.3±0.04
`6.0± 0.07
`6.4 ± 0.04
`5.7 ± 0.08
`9.1±0.04
`6.0 ± 0.08
`
`6.8 ± 0.04
`6.7 ± 0.05
`6.6 ± 0.02
`6.3 ± 0.06
`6.6 ± 0.03
`6.2 ± 0.09
`6.3 ± 0.10
`9.2 ±0.09
`6.0 ± 0.05
`
`a Values expressed as mean± S.D. for three determinations.
`b PVC
`polyvinyl chloride.
`c Medital, Ede, The Netherlands, lot 86 K 17-4234.
`
`in the PVC container (Table 2), decreasing 15%
`within two hours and 55% at 24 hours. The sorption
`of diazepam to PVC has been reported previous-
`: ly.1,3,4,6,7 Cloyd et al. 6 reported a reduction in diaze(cid:173)
`. pam concentration of about 55% in 24 hours. No
`sorption of diazepam was observed to occur in
`Clear-Flex or glass containers over at least 24 hours.
`Isosorbide dinitrate showed a 23% decrease in
`concentration after 24 hours of storage in the PVC
`containers (Table 2). Most of the decrease occurred
`during the first six hours (15% loss). Similar results
`were found by Lee and Fenton-May,8 who report(cid:173)
`ed that isosorbide dinitrate is stable in PVC for
`only two hours and that after 24 hours the loss is
`about 30%. We observed no marked decrease of
`isosorbide dinitrate in Clear-Flex or glass contain(cid:173)
`ers.
`Nitroglycerin retained potency for at least 24
`hours in Clear-Flex and glass containers. As expect(cid:173)
`ed, nitroglycerin was incompatible with PVC.4,9,10
`A 10% decrease was seen after 1 hour, and after 24
`hours only 49% of the initial concentration was
`measured (Table 2). This is in agreement with the
`results of Baaske et al.,9 who reported a 42% de(cid:173)
`crease in nitroglycerin concentration after 24
`hours of storage in PVC containers at room tem(cid:173)
`perature.
`Warfarin sodium did not show any sorption in
`Clear-Flex and glass containers. However, warfa(cid:173)
`rin sodium concentration decreased 24% after 24
`hours of storage in PVC containers (Table 2). These
`results conflict with those of Kowaluk et al., 1 who
`found that warfarin sodium (22 µg/mL, pH 6.7)
`was stable after 24 hours and that only 15% was lost
`after one week.
`Unlike Kowaluk et al.,1 we did not observe any
`decrease in thiopental sodium concentration in
`PVC containers. This can be explained by differ(cid:173)
`ences in the methods used. In our study the con(cid:173)
`centration of the test solution was 2000 µg/mL to
`represent a therapeutic dosage (Table 2), while
`Kowaluk et al. used a concentration of 7 µg/mL,
`
`which allowed direct spectrophotometric assay
`without further dilution. This resulted in a negligi(cid:173)
`ble loss of thiopental sodium at pH 9.1, as in our
`study, but a 15% loss at pH 6.0.1 The differences can
`be explained by the different pH values. For an
`acidic drug like thiopental sodium, sorption is fast(cid:173)
`er at low pH because a greater fraction of the drug
`is nonionized. It seems that the concentration-de(cid:173)
`pendent sorptive process for thiopental sodium
`suggested by Kowaluk et al. is dependent on solu(cid:173)
`tion pH rather than on a saturable sorptive process.
`The loss of chloroquine hydrochloride due to
`sorption reported by Geary et al.,11 30-40% of a 32-
`µg / mL solution in glass test tubes, was not con(cid:173)
`firmed in our study. Whether this discrepancy is
`the result of a difference in chloroquine formula(cid:173)
`tion or glass quality can be resolved only by further
`investigation.
`
`Conclusion
`
`Diazepam, isosorbide dinitrate, nitroglycerin,
`and warfarin sodium in 0.9% sodium chloride in(cid:173)
`jection showed a loss of potency when stored in
`PVC containers for 24 hours at room temperature,
`but none of the drugs studied lost potency when
`stored in glass bottles and Clear-Flex bags.
`
`a Viaflex, Baxter, Utrecht, The Netherlands, lot 87 A 07 A4.
`b Medital, Ede, The Netherlands, lot 86102205; also available
`as Soluflex; not available in the United States.
`c Lansberg, Uden, The Netherlands, lot 86 K 17-4234.
`d Nivaquine 100 mg/2 mL, Rhone-Poulenc, Amstelveen, The
`Netherlands, lot 82J13-101.
`e Diazepam injection 10 mg/2 mL, Centrachemie, Ettenleur,
`The Netherlands, lot 8SL28A.
`f Cedocard 10 mg/ 10 mL, Cedona, Haarlem, The Nether(cid:173)
`lands, lot 86113.
`g Temesta 4 mg/mL, Wyeth, Hoofddorp, The Netherlands,
`lot 87818-7013.
`h Dormicum 5 mg/mL, Hoffmann-LaRoche, Mijdrecht, The
`Netherlands, lot bo28-86J22.
`i Nitroglycerin-Pohl 50 mg/10 mL, Tramedico, Weesp, The
`Netherlands, lot 85119.
`
`372 American Journal of Hospital Pharmacy Vol 47 Feb 1990
`
`Hospira, Exh. 2020, p. 4
`
`

`
`Sorption of drugs to containers. Reports
`
`i Promethazine hydrochloride injection 50 mg/2 mL, own
`pharmacy production, lot 86L15-61.
`k Warfarin sodium injection 2 mg/mL, own pharmacy pro(cid:173)
`duction, lot 86H15-63.
`1 Nesdonal, Specia, Amstelveen, The Netherlands, lot 86F24-
`6541-1.
`m Monoject, s'Hertogenbosch, The Netherlands, lot 86El5.
`n Salm en Kipp, Breukelen, The Netherlands.
`0 Waters Associates, Etten-Leur, The Netherlands.
`P Chrompack-Packard, Middelburg, The Netherlands.
`q Merck, Amsterdam, The Netherlands.
`
`References
`1. Kowaluk EA, Roberts MS, Blackbum HD et al. Interactions
`between drugs and polyvinyl chloride infusion bags. Am J
`Hosp Pharm. 1981; 38:1308-14.
`2. D' Arey PF. Drug interactions with medical plastics. Drug
`lntell Clin Pharm. 1983; 17:726-31.
`3. Moorhatch P, Chiou WL. Interactions between drugs and
`plastic intravenous fluid bags. Part i: sorption studies on 17
`diugs. Am/ Hosp Pharm. 1974; 31:72-8.
`
`4. Gerard LM. Sorption of four drugs to polyvinyl chloride
`and polybutadiene intravenous administration sets. Am /
`Hosp Pharm. 1986; 43:1945-50.
`5. Anon. Clear-Flex scientific information and bibliography.
`Lugano, Switzerland: Medital; 1987.
`6. Cloyd JC, Vezeau C, Miller KW. Availability of diazepam
`from plastic containers. Am J Hosp Pharm. 1980; 37:492-6.
`7. Yliniusi JK, Uotila JA, Kristoffersson ER. Effect of flow rate
`and type of i.v. container on adsorption of diazepam to i.v.
`administration systems. Am/ Hosp Pharm. 1986; 43:2795-9.
`8. Lee MG, Fenton-May V. Absorption of isosorbide dinitrate
`by PVC infusion bags and administration sets. J Clin Hosp
`Pharm. 1981; 6:209-11.
`9. Baaske OM, Amann AH, Wagenknecht DM et al. Nitro(cid:173)
`glycerin compatibility with intravenous fluid filters, con(cid:173)
`tainers, and administration sets. Am J Hosp Pharm. 1980;
`37:201-5.
`10. De Rudder D, Remon JP, Neyt EN. The sorption of nitro(cid:173)
`glycerin by infusion sets./ Pharm Pharmacol. 1987; 39:556-8.
`11. Geary TG, Akood MA, Jensen JB. Characteristics of chloro(cid:173)
`quine binding to glass and plastic. Am J Trop Med Hyg. 1983;
`32:19-23.
`
`f7ecovery of phenytoin suspension after in vitro
`administration through percutaneous endoscopic
`· gastrostomy Pezzer catheters
`MICHELE Y. SPLINTER, CHARLES F. SEIFERT, J. CHRISTOPHER BRADBERRY, LOYD V. ALLEN, JR.,
`Yu-HSING Tu, AND JACK D. WELSH
`
`Abstract: Various methods of ad(cid:173)
`ministering phenytoin suspension
`through a percutaneous endoscopic
`gastrostomy (PEG) Pezzer catheter
`were evaluated in vitro to determine
`which method resulted in the most
`complete recovery of phenytoin.
`To determine the effect of tem(cid:173)
`perature on phenytoin recovery, 12
`mL of phenytoin suspension (Di(cid:173)
`lantin-125, 125 mg/5 mL) was ad(cid:173)
`ministered through three separate
`35.5-cm 20 French latex PEG Pezzer
`catheters under each of three tem(cid:173)
`perature conditions (suspension
`11.8 °C and catheter 22 °C, suspen(cid:173)
`sion and catheter 22 °C, and sus(cid:173)
`pension 22 °C and catheter 37 °C).
`To determine the effect of the ad-
`
`ministration method, 12-mL ali(cid:173)
`quots of phenytoin suspension
`were injected into the catheter by
`seven methods that varied with re(cid:173)
`spect to catheter temperature, dih1-
`tion of suspension, and irrigation of
`catheter. Each method was tested iri
`triplicate, and samples were as(cid:173)
`sayed by high-performance liquid
`chromatography.
`Varying the temperature of the
`catheter or suspension had little ef(cid:173)
`fect on the recovery of phenytoin.
`There was no appreciable loss of
`phenytoin when the suspension
`was undiluted, regardless of
`whether the catheter was irrigated.
`The greatest losses were seen when
`the suspension was diluted before
`
`administration. Irrigation also
`caused a decrease in recovery, but
`to a lesser extent than dilution.
`µntil the effects of administering
`multiple doses of phenytoin
`through PEG Pezzer catheters are
`investigated, phenytoin suspen(cid:173)
`sion should not be diluted before
`administration because of de(cid:173)
`creased recovery and increased ad(cid:173)
`ministration time.
`
`Index terms: Adsorption; Anticon(cid:173)
`vulsan ts; Catheters; Dilutions;
`. Drug administration; Drug admin(cid:173)
`istration routes; Incompatibilities;
`Irrigation; Latex; Phenytoin; Stabil(cid:173)
`ity; Suspensions; Temperature
`Am J Hosp Pharm. 1990; 47:373-7
`
`MICHELE Y. SPLINTER, M.S., is Dispensing Coordinator, De(cid:173)
`partment of Pharmacy Services, Oklahoma Memorial Hospital,
`Oklahoma City, OK; at the time of this study, she was Surgery
`Satellite Pharmacist, Pepartment of Pharmaceutical Services,
`South Community Hospital, Oklahoma City. CHARLES F. SEI(cid:173)
`FERT, PHARM.D., is Assistant Professor of Adult Medicine, Sec(cid:173)
`tion of Pharmacy Practice, College of Pharmacy; J. CHRISTO(cid:173)
`PHER BRADBERRY, PHARM.D., is Professor and Head, Section of
`Pharmacy Practice; LOYD V. ALLEN, JR., PH.D., is Professor and
`Head, Section of Pharmaceutics, College of Pharmacy; Yu(cid:173)
`HSING Tu, PH.D., is Research Associate, Section of Pharmaceu(cid:173)
`tics; and JACK D. WELSH, M.D., is Professor and Chief, Division
`of Digestive Diseases and Nutrition, College of Medicine, Uni(cid:173)
`versity of Oklahoma Health Sciences Center, Oklahoma City.
`
`Address reprint requests to Dr. Seifert at the Section of Phar(cid:173)
`macy Practice, College of Pharmacy, University of Oklahoma
`Health Sciences Center, 1110 N. Stonewall, P.O. Box 26901,
`Oklahoma City, OK 73190.
`The assistance of Elisa T. Lee, Ph.D., with statistical analysis
`and of Robert A. Magarian, Ph.D., and the Section of Medicinal
`Chemistry and Pharmacodynamics in allowing the u5e of their
`instrumentation for HPLC analysis is acknowledged.
`Presented in part at the 22nd Annual ASHP Midyear Clinical
`Meeting, Atlanta, GA, December 10, 1987.
`
`Copyright © 1990, American Society of Hospital Pharmacists,
`Inc. All rights reserved. 0002-9289/90/0201-0373$01.25.
`
`Vol 47 Feb 1990 American Journal of Hospital Pharmacy 373
`
`Hospira, Exh. 2020, p. 5