Zidovudine
osine) have not shown unexpected adverse effects [7–10].
See also Nucleoside analogue reverse transcriptase
inhibitors (NRTIs)
GENERAL INFORMATION
Zidovudine is a nucleoside analogue reverse transcriptase
inhibitor. Its adverse effects include hematological com-
plications, severe headache, insomnia, confusion, nausea,
vomiting, abdominal discomfort, myalgia (myopathy), and
nail pigmentation [1].
DRUG STUDIES
Observational studies
Oral zidovudine in a dosage of 200 mg every 4 hours for 42
days was used as prophylaxis in health-care workers after
percutaneous exposure to blood or body fluids from HIV-
infected patients. Adverse reactions occurred in 73%, the
most frequent being nausea (47%), headache (35%), and
fatigue (30%). Of selected hematological laboratory
markers only platelet counts increased significantly over
4 weeks. Although adverse reactions were not very severe
and none of the laboratory changes was considered clini-
cally significant, treatment was poorly accepted and
stopped prematurely by 30% [2]. Current guidelines for
postexposure prophylaxis recommend a much lower dos-
age (300 mg bd) with much better tolerance [3].
In a retrospective study of patients co-infected with
HIV and hepatitis C who were given peginterferon þ
ribavirin and concurrent zidovudine, significant anemia,
defined as a loss of >25% of hemoglobin concentration
over the first 4 weeks of therapy, was associated with
zidovudine (OR ¼4.4; 95% CI ¼2.3, 8.5) [4].
Comparative studies
The safety and efficacy of lamivudine (300–600 mg/day) in
combination with zidovudine (600 mg/day) in the treatment
of antiretroviral-naive and zidovudine-experienced HIV-
infected persons has been compared with zidovudine
monotherapy in two placebo-controlled studies of 129 and
223 patients [5,6]. There were no significant differences in
the incidence or severity of adverse effects between
patients taking zidovudine alone or in combination with
lamivudine. In both studies gastrointestinal symptoms,
notably nausea, were the most commonly observed adverse
reactions, occurring in 5–11% of zidovudine-experienced
patients and 23–29% of antiretroviral drug-naive individ-
uals. Although one antiretroviral drug-naive patient taking
combined therapy had an asymptomatic rise in pancreatic
amylase activity, acute pancreatitis was not observed in
either study. Grade 1 peripheral neuropathy was reported
in one zidovudine-experienced patient taking low-dosage
lamivudine (150 mg bd) and zidovudine.
Several large-scale studies of the efficacy of combined
antiretroviral treatment with zalcitabine and zidovudine
in HIV-infected patients (compared with zidovudine
ã 2016 Elsevier B.V. All rights reserved.
monotherapy or a combination of zidovudine and didan-
The most common adverse reactions in patients taking
zalcitabine were peripheral neuropathy and aphthous
mouth ulcers.
ORGANS AND SYSTEMS
Nervous system
Various nervous system adverse reactions to zidovudine
have been reported, which may or may not be directly
related to the drug. These include seizures, confusion,
and acute encephalopathy occurring after zidovudine dos-
age reduction [11].
Palpebral ptosis in a patient taking zidovudine was
attributed to mitochondrial toxicity from zidovudine; it
resolved when the treatment was changed [12].
Metabolism
Weight gain has been used as a marker of recovery from
stavudine-associated lipoatrophy in 114 Rwandan women
[13]. Replacement with tenofovir þ abacavir was associ-
ated with a progressive increase in weight, but zidovudine
was associated with progressive weight loss.
Lipodystrophy is a common adverse reaction to antire-
troviral drugs, particularly the NRTIs and has been
reported with zidovudine [14].
 A 42-year-old woman developed abdominal and dorsocervical
fat enlargement after having taken zidovudine for over 10
years. Zidovudine was withdrawn and the lesions improved
considerably over the next 26 months.
The differential effects of antiretroviral drugs on body fat
disposition have been studied in 50 HIV-1 infected men in
a randomized single-blind comparison of zidovudi-
ne þ lamivudine with lopinavir þ ritonavir and nevirapine
with lopinavir þ ritonavir [15]. In those who took the
zidovudine-based therapy limb fat fell progressively from
3 months onward by a mean of 684 g up to 24 months,
whereas abdominal fat increased, but exclusively in the
visceral compartment. In contrast, in those who took
nevirapine-based therapy there was a generalized increase
in fat mass. After 24 months there were no significant
differences in HDL cholesterol and the total/HDL choles-
terol ratio, but total and LDL cholesterol were higher in
those who had taken nevirapine.
The mechanism whereby zidovudine is antiadipogenic
has been studied in 3 T3-F442A preadipocytes, which
were exposed to zidovudine (1, 3, 6, and 180 mmol/l),
stavudine (3 mmol/l), and zalcitabine (0. 1 mmol/l) for up
to 15 days [16]. When they were induced to differentiate in
the presence of zidovudine, the cells failed to accumulate
cytoplasmic triacylglycerol and failed to express normal
amounts of the later adipogenic transcription factors,
CCAAT/enhancer-binding protein alpha and peroxisome
proliferator-activated receptor gamma. Zidovudine inhib-
ited the completion of the mitotic clonal expansion, which
resulted in incomplete cell differentiation and a reduction
in the degree of adiponectin expression. It also impaired

constitutive proliferation. In contrast, zalcitabine and
stavudine had no effects.
In a study of subcutaneous fat samples from 32 HIV-
positive treatment-naı̈ve patients before and 6 months after
randomization to zidovudine þ lamivudine þ efavirenz (n
¼15) or tenofovirþ emtricitabine þ efavirenz (n ¼17) and
15 HIV-negative matched controls, the expression of genes
involved in adipocyte differentiation, lipid metabolism,
mitochondrial function, and glucocorticoid generation
were profiled using real-time PCR [17]. Lipoprotein lipase
and hepatic lipase activity were assessed before treatment.
Zidovudine was associated with significant increases in
visceral adipose tissue and the ratio of visceral adipose
tissue to subcutaneous adipose tissue, down-regulation of
cytochrome B and cytochrome oxidase-3 gene expression,
and up-regulation of NADH dehydrogenase and nuclear-
encoded cytochrome oxidase-4 (complex IV) gene expres-
sion. Genes involved in adipocyte cortisol generation, fatty
acid metabolism, and the tricarboxylic acid cycle were up-
regulated. In those who took tenofovir, there were no
significant changes in regional body fat or mitochondrial
genes. Changes in the expression of genes involved with
cortisol and fatty acid metabolism were less marked with
tenofovir.
In a 48-week, open, randomized comparison of continu-
ation of twice-daily zidovudine þ lamivudine or replace-
ment with once-daily tenofovir þ emtricitabine in 100
individuals taking successful efavirenz-based antiretroviral
therapy, limb fat mass was assessed by dual x-ray absorpti-
ometry [18]. Fat was preserved or increased in the switch
group but fell in the continuation group (mean difference
448 g, 95% CI ¼57, 839). The loss of limb fat was attributed
to zidovudine.
Adverse reactions to nucleoside reverse transcriptase
inhibitors, including myopathies, lactic acidosis, and periph-
eral neuropathy, have been associated with inhibition of
human mitochondrial DNA polymerase g [19–21], and an
autosomal recessive mutation, arginine 964 to cysteine
(R964C), has been suggested to confer a predisposition to
stavudine-induced mitochondrial toxicity. In steady-state
enzyme kinetic studies, the R964C polymerase g holoen-
zyme was only 67% efficient in incorporating deoxythy-
midine triphosphate (dTTP), its natural substrate, and
three times less discriminatory for 2’,3’-didehydro-3’-
deoxythymidine-5’-triphosphate (d4TTP), the active phos-
phorylated metabolite of stavudine (d4T), relative to the
wild-type enzyme [22].
Lipoatrophy due to long-term use of zidovudine and
stavudine may occur through different mechanisms. Sur-
gical biopsies from 18 HIV-1 patients, 10 of whom were
taking zidovudine and 8 stavudine, showed that zidovu-
dine was associated with lower adipogenesis gene expres-
sion, while stavudine was associated with significantly
lower expression of genes associated with mitochondrial
biogenesis. [23]
Hematologic
The main dose-limiting adverse reactions of zidovudine
therapy in HIV-infected adults and children are hemato-
logical complications [24]. When zidovudine was intro-
duced it was given in about twice the dosage used today.
ã 2016 Elsevier B.V. All rights reserved.
Zidovudine 557
Consequently, hematological adverse reactions occur at a
much lower frequency than previously reported [25,26].
Almost uniformly, zidovudine treatment results in a
progressive increase in the erythrocyte mean cell volume,
which cannot be prevented by supplementation with vita-
min B12 and folinic acid [27]. Zidovudine can cause ane-
mia [28] and reversible pure red cell aplasia [29]. While
recombinant erythropoietin is useful in correcting
zidovudine-induced anemia, some cases of anemia are
associated with high serum erythropoietin concentrations
and normocytic cells, indicating bone marrow unrespon-
siveness to erythropoietin [30]. Measuring baseline serum
erythropoietin concentrations may help to predict the
response to this very costly hormone supplementation.
The rate of anemia in infants born to mothers receiving
zidovudine for prevention of mother-to-child transmission
was slighter higher than in those born to mothers receiving
other nucleoside analogues [31].
Hypoproliferative anemia is a typical, severe adverse
effect of zidovudine; it usually resolves promptly after
withdrawal of the drug. However, three patients devel-
oped zidovudine-induced anemia that could have been
mistaken for hemolytic disease, especially in the first 2
weeks after withdrawal of the drug [32].
Pure red cell aplasia occurred in a 27-year-old woman
who had taken zidovudine, lamivudine, and nevirapine for
1 year; it resolved when zidovudine was replaced by stav-
udine [33].
In an Indian study of 98 HIV-positive patients there
were 19 cases of zidovudine-associated anemia. A baseline
hemoglobin concentration below 10.5 g/dl was a suscepti-
bililty factor [34].
In neonates receiving postnatal zidovudine prophylaxis
after prenatal exposure to HAART with (n ¼44) or with-
out zidovudine (n ¼21) there were significantly lower
hemoglobin, red cell counts, and hematocrit and a higher
MCV at birth in those who had been exposed to zidovu-
dine [35]. However by 4 weeks of postnatal zidovudine
prophylaxis there was no difference between the two
groups.
Hemoglobin A2 can rise in HIV-infected patients, pos-
sibly because of therapy [36]. In cross-sectional and cohort
studies hemoglobin A2 was often raised in untreated
patients but a further rise during treatment was specifi-
cally attributable to zidovudine. The concentration of
hemoglobin A2 may be high enough to lead to a misdiag-
nosis of beta-thalassemia.
Of 1089 adults taking stavudine-containing HAART
(median observation time, 3 years), 290 (27%) had zido-
vudine substituted for didanosine, after which there were
higher frequencies of anemia and leukopenia [37]. Con-
versely, in 158 patients taking zidovudine, 77 of whom
switched to another drug, the switch occasioned a net
increase in hemoglobin of 1.1 g/dl and a net increase in
neutrophil count of 541  106/l [38].
Zidovudine can cause neutropenia [28].
Thrombocytopenia has been observed in patients using
zidovudine and didanosine [39,40].
In 740 adults who were given zidovudine þ
lamivudine þ efavirenz, 28 interrupted treatment because
of zidovudine-attributable adverse reactions, including 25
with severe anemia, two with severe neutropenia, and one
with non-obstructive cardiomyopathy [41].
558 Zidovudine
Skin
Fatal toxic epidermolysis has been attributed to zidovu-
dine [42] as has cutaneous hypersensitivity [43].
Zidovudine can occasionally cause unusual pigmenta-
tion, probably depending on the individual’s pigmentary
pattern [44].
Nails
The presenting sign of neutropenia in a neonate treated with
prophylactic zidovudine for reduction of perinatal transmis-
sion was, unusually, severe paronychia of the large toes as a
result of Candida albicans and Escherichia coli infection
[45]. The paronychia resolved after treatment with oral
fluconazole and topical antiseptics. Paronychia of the large
toes has also been observed when filgrastim (recombinant
granulocyte colony stimulating factor) was used alongside
chemotherapy in poor-risk patients with myelodysplastic
syndrome [46], and there is some evidence that paronychia
(even in the absence of blood disorders) can occur as an
independent adverse reaction to various antiretroviral
drugs, including indinavir and lamivudine [47].
Closely similar is the strong evidence from case–control
studies that ingrowing toenails are associated with the use
of indinavir [48] and possibly other similar compounds,
but not lamivudine.
Musculoskeletal
Myopathy has been well described with long-term zidovu-
dine and is reversible after withdrawal [49]. Phosphorus
magnetic resonance spectroscopy has been used to study
the changes in phosphorylated metabolites (ATP, phos-
phocreatine, and inorganic phosphate) during exercise in
19 healthy volunteers, 6 untreated HIV-positive individ-
uals, and 9 zidovudine-treated patients with biopsy-
proven myopathy [50]. Zidovudine altered the normal
muscle energy metabolism in the patients with myopathy,
suggesting that it reduces maximal work output, and thus
the maximal rate of mitochondrial ATP synthesis, in
human muscle. So far, the syndrome has not been associ-
ated with any other NRTI [51] and it has been suggested
that other factors might contribute to the development of
zidovudine-associated myopathy [52]. Mitochondrial
abnormalities have also been observed in biopsies from
untreated patients infected with HIV-1, suggesting that
the virus itself can also cause myopathy.
To assess the contribution of zidovudine to the mito-
chondrial damage, the effects of zidovudine on non-
infected co-cultures of spinal ganglia, spinal cord, and
skeletal muscle in fetal rats have been studied [53].
There were significant changes not only in the mitochon-
dria but also in the nuclei of all cells tested. These changes
depended less on the concentration of zidovudine than on
the duration of exposure.
Changes in bone mineral density and bone turnover
have been studied in 50 patients taking lopinavir þ
ritonavir with either zidovudineþ lamivudine or nevirapine
[54]. Bone mineral density rapidly fell in both the fem-
oral neck and lumbar spine after the start of therapy, and
there was greater loss after 24 months in those who took
ã 2016 Elsevier B.V. All rights reserved.
zidovudine þ lamivudine. Osteocalcin and the urine deox-
ypyridinoline:creatinine ratio increased to the same extent
in both groups. Changes in parathyroid hormone did not
explain the greater bone loss with zidovudine þ lamivudine.
In a comparison of changes in bone mineral density in
106 HIV-1 infected, antiretroviral drug-naive patients,
who were randomized to zidovudine þ lamivudine with
either efavirenz (n ¼32) or lopinavir þ ritonavir (n ¼74)
for 96 weeks, the mean changes from baseline in total
bone mineral density were 2.5% (lopinavir þ ritonavir)
and 2.3% (efavirenz) [55]. The authors concluded that
loss of bone mineral density during antiretroviral drug
therapy is independent of the drug regimen.
Multiorgan failure
A well-documented case has shown that zidovudine can
cause type B lactic acidosis and acute respiratory and
hepatic failure [56].
 A 34-year-old obese woman developed nausea, vomiting, and
intermittent diarrhea. Her current medications included zido-
vudine. She had tachypnea and tender hepatomegaly, and a CT
scan of the abdomen showed hepatomegaly with fatty infiltra-
tion. The serum bicarbonate concentration was low and the
lactate concentration three times normal. The tachypnea and
dyspnea worsened as the lactate concentration rapidly
increased to 15 times normal, and she died in acute respiratory
and hepatic failure with multiorgan dysfunction.
LONG-TERM EFFECTS
Genotoxicity
Micronucleated reticulocyte frequencies have been mea-
sured as a marker of chromosomal damage in 16 HIV-
infected mother-infant pairs, of whom 13 women had
taken prenatal zidovudine and three antiretroviral drugs
without zidovudine [57]. All the infants received zidovu-
dine for 6 weeks. Venous blood was obtained from women
at delivery and from infants at 1–3 days, 4–6 weeks, and
4–6 months of life; cord blood was collected immediately
after delivery. Ten cord blood samples (controls) were
obtained from infants of HIV-negative women who did
not receive antiretroviral therapy. There were 10-fold
increases in micronucleated reticulocytes in women and
infants who received zidovudine-containing antiretroviral
therapy prenatally and no increases in the other women
and infants. Micronucleated reticulocytes in the
zidovudine-exposed neonates fell over the first 6 months
of life to values comparable to cord-blood controls. The
authors concluded that transplacental zidovudine expo-
sure is genotoxic in humans and they recommended
long-term monitoring of zidovudine-exposed infants.
SECOND-GENERATION EFFECTS
Pregnancy
Zidovudine is relatively well tolerated in pregnancy, with
anemia, neutropenia, or thrombocytopenia occurring in

10% and abnormalities of serum electrolytes and liver
function in 5% and no increased incidence of neonatal
structural abnormalities [58].
In a pharmacokinetic study of three doses of zidovudine
300 mg 3-hourly in pregnancy in six subjects plasma zido-
vudine concentrations were substantially lower than pre-
viously reported during continuous intravenous therapy
[59]. In another study in four women who took an initial
600 mg dose followed by two 400 mg doses 3-hourly the
zidovudine AUC and concentrations increased approxi-
mately in proportion to the increase in dose but varied 6–7
times [60]. In both cohorts, the pharmacokinetic results
suggested erratic absorption.
Teratogenicity
There has been a randomized cohort study in the USA of
children from 122 pregnancies in which zidovudine was
given and of children from 112 pregnancies in which only
a placebo was used [61]. The median age of the children at
the last follow-up visit was 4.2 years. There were no signif-
icant differences between children exposed to zidovudine
and those who received placebo in terms of sequential data
on lymphocyte subsets, weight, height, head circumference,
and cognitive/developmental function. There were no
deaths or malignancies. Two children (both exposed to
zidovudine) were still being followed for unexplained
abnormal fundoscopy. One child exposed to zidovudine
had a mild cardiomyopathy on echocardiography at the
age of 48 months but was clinically asymptomatic.
A possible association between first trimester exposure
to zidovudine and an increased risk of hypospadias based
on one cohort study has been reported [62]. Among 2527
live births to 2353 women defects were identified in 90
babies (3.56 defects per 100 live births). The rate of defects
was 3.19 per 100 live births with first-trimester antiretro-
viral drug exposure, 3.54 per 100 live births with exposure
later in pregnancy, and 4.05 of 100 live births with no
antiretroviral drug use. Only genital abnormalities, specif-
ically hypospadias, were significantly increased among
babies born to women with first-trimester exposure to
antiretroviral drugs (7 of 382 male live births) compared
with the two other groups (2 of 892 male live births).
Logistic regression suggested that use of zidovudine in
the first trimester was associated with hypospadias
(adjusted OR ¼11; 95% CI ¼2.1, 54).
Lactation
Since zidovudine seems to be relatively well tolerated both
in pregnancy and in neonates, there is also much reason to
consider its use during lactation in order to reduce vertical
transmission of HIV. Indeed, many would regard it as highly
preferable to abandoning breastfeeding by HIV-infected
women. In a critical double-blind West African study the
effects of a 6-month course of treatment in prenatal and
lactating mothers were examined [63]. Eligible participants
were women aged 18 years or older who had confirmed
HIV-1 infection, were 36–38 weeks pregnant, and gave writ-
ten informed consent. Exclusion criteria were severe ane-
mia, neutropenia, abnormal liver function, and sickle cell
ã 2016 Elsevier B.V. All rights reserved.
Zidovudine 559
disease. They were randomly assigned to zidovudine (n
¼214; 300 mg bd until labor, 600 mg at the start of labor,
and 300 mg bd for 7 days) or to matching placebo (n ¼217).
The Kaplan-Meier probability of HIV infection in the infant
at 6 months was 18% in the zidovudine group and 28% in the
placebo group, a relative efficacy of 0.38. In current and
follow-up observations over 6 months, no major adverse
biological or clinical events were reported in excess among
women or children in the zidovudine group. The authors
concluded that a short course of oral zidovudine given dur-
ing the peripartum period is well tolerated and provides
significant reduction in early vertical transmission of HIV-1
infection despite breastfeeding.
A second related study showed similar results [64], and
the two papers together provide impressive evidence that
it is proper and defensible to use zidovudine in breastfeed-
ing mothers.
SUSCEPTIBILITY FACTORS
Age
The only recognized toxic effect in infants is anemia
within the first 6 weeks of life, which is not associated
with premature delivery, duration of maternal treatment,
degree of maternal immunosuppression, or maternal ane-
mia. An 18-month follow-up of 342 children born to
mothers who had taken zidovudine or placebo during
pregnancy has recently been reported [65]. There were
no differences in growth parameters or immune function
in uninfected children. In addition, no childhood neopla-
sias were reported in either group.
DRUG ADMINISTRATION
Drug overdose
A 4-day-old boy who was inadvertently given two 10-fold
overdoses of zidovudine developed a transient lactic aci-
dosis, a slight rise in aspartate aminotransferase, and a
neutropenia that persisted for 5 weeks [66].
DRUG–DRUG INTERACTIONS
See also Inosine pranobex; Interferon alfa; Nelfinavir;
Valproic acid
Atovaquone
Atovaquone can potentiate the activity of zidovudine by
inhibiting its glucuronidation [67,68].
Azithromycin
Zidovudine does not affect azithromycin concentrations
and azithromycin does not affect zidovudine concentra-
tions [69].
560 Zidovudine

Clarithromycin Oxazepam
Clarithromycin has an unpredictable effect on the absorp- There was a striking incidence of headache in a small
tion of zidovudine; blood concentrations may rise or fall series of patients when zidovudine was given with oxaze-
[70,71]. pam [77].

Co-trimoxazole
Combined exposure to zidovudine plus co-trimoxazole
caused a clinically significant suppression of humoral
immune responses to influenza immunization in 23 HIV-
positive patients with CD4 counts above 350  106/l [72].
Cytotoxic drugs
In 13 HIV-infected patients with cancer, the mean phar-
macokinetics of zidovudine (AUC, half-life, oral clear-
ance, and oral apparent volume of distribution) were no
different with or without chemotherapy [73]. However,
there was a 57% reduction in Cmax and a 66% increase
in tmax after chemotherapy. There were no differences in
the urinary excretion of zidovudine or zidovudine glucu-
ronide. The authors concluded that these minor changes
did not warrant any change in the dosage of zidovudine
during concurrent chemotherapy.
Fluconazole
Zidovudine glucuronidation in human hepatic micro-
somes in vitro was inhibited more by the combination of
fluconazole with valproic acid than with other drugs, such
as atovaquone and methadone [67].
Paracetamol
Concomitant administration of paracetamol and zidovu-
dine leads to inhibition of glucuronidation and to potenti-
ation of the toxicity of each drug [78–80].
Probenecid
Probenecid reduces the renal tubular secretion of zidovu-
dine [81].
In two healthy volunteers, co-administration of proben-
ecid 500 mg every 6 hours altered the pharmacokinetics of
a single oral dose of zidovudine 200 mg [82]. There was an
increase in the average AUC, with a corresponding reduc-
tion in oral clearance, attributed to an inhibitory effect of
probenecid on the glucuronidation and renal excretion of
zidovudine.
Eight subjects took zidovudine for 3 days with and with-
out probenecid 500 mg every 8 hours for 3 days, and then
additional quinine sulfate 260 mg every 8 hours [83]. Pro-
benecid increased the AUC of zidovudine by 80%. Quinine
prevented the probenecid effect but had no effect on zido-
vudine kinetics when it was taken without probenecid by
four other subjects. All of the effects were secondary to
changes in zidovudine metabolism, since neither probene-
cid nor quinine changed the renal elimination of zidovudine.

Ribavirin
Ganciclovir
Ribavirin did not inhibit the formation of zidovudine tri-
Zidovudine and ganciclovir have overlapping toxicity pro- phosphate in peripheral blood monocytes in 14 patients
files with respect to adverse hematological effects. Severe over 8 weeks [84].
life-threatening hematological toxicity has been reported
in 82% of patients treated with a combination of zidovu-
dine and ganciclovir [74]. The combination of ganciclovir Rifamycins
with didanosine was much better tolerated [75].
Rifampicin, a well-known enzyme inducer, increased the
metabolism of zidovudine, and the effect persisted for 2
weeks after rifampicin had been withdrawn [85].
Methadone
The metabolism of the antiviral nucleoside zidovudine to
the inactive glucuronide form in vitro was inhibited by Trimethoprim and co-trimoxazole
methadone [67]. The concentration of methadone
In one pharmacokinetic study in eight HIV-infected sub-
required for 50% inhibition was over 8 mg/ml, a suprather-
jects, the renal clearance of zidovudine was significantly
apeutic concentration, thus raising questions about the
reduced by trimethoprim [86]. The authors concluded that
clinical significance of the effect. However, in eight
zidovudine dosages may need to be reduced if trimetho-
recently detoxified heroin addicts, acute methadone treat-
prim is given to patients with impairment of liver function
ment increased the AUC of oral zidovudine by 41% and
or glucuronidation. Zidovudine, on the other hand, did
of intravenous zidovudine by 19%, following the start of
not alter the pharmacokinetics of trimethoprim.
oral methadone (50 mg/day) [76]. These effects resulted
primarily from inhibition of zidovudine glucuronidation,
but also from reduced renal clearance of zidovudine, and
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